Diagnosis Of Alzheimer's Disease Patients Research Articles

Cost-effectiveness of Alzheimer's disease CSF biomarkers and amyloid-PET in early-onset cognitive impairment diagnosis.

This study aimed at determining the cost-effectiveness of amyloid-positron emission tomography (PET) compared to Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid-β42, total-Tau and phosphorylated-Tau) for the diagnosis of AD in patients with early-onset cognitive impairment. A decision tree model using a national health care perspective was developed to compare the costs and effectiveness associated with Amyloid-PET and AD CSF biomarkers. Available evidence from the literature and primary data from Hospital Clínic de Barcelona were used to inform the model and calculate the efficiency of these diagnostic alternatives. Medical visits and diagnostic procedures were considered and reported in €2020. We calculated the incremental cost-effectiveness ratio to measure the cost per % of correct diagnoses detected and we perform one-way deterministic and probabilistic sensitivity analyses to assess the uncertainty of these results. Compared with AD CSF biomarkers, Amyloid-PET resulted in 7.40% more correctly diagnosed cases of AD, with an incremental total mean cost of €146,854.80 per 100 cases. We found a 50% of probability that Amyloid-PET was cost-effective for a willingness to pay (WTP) of €19,840.39 per correct case detected. Using a WTP of €75,000, the probability that it is cost-effective reached a maximum of 76.9%, thus leading to a conclusion that Amyloid-PET is not a cost-effective technique compared to AD CSF biomarkers, unless the funder is willing to pay a minimum of €19,840.39 to detect one morecorrect case. Furthermore, obtaining CSF provides simultaneous information on amyloid β and tau biomarkers and allows other biomarkers to be analyzed at a relatively low cost.

Abnormal baseline brain activity in Alzheimer's disease patients with depression: a resting-state functional magnetic resonance imaging study.

As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood. The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients. The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients. These findings may provide further insight into the underlying neuropathophysiology of AD with depression.

A Comparison of the Behavioral and Psychological Symptoms of Dementia (BPSD) in Early-Onset and Late-Onset Alzheimer's Disease - A Study from South East Asia (Kashmir, India).

BackgroundA gradual increase in the longevity due to advancement of treatment modalities and a subsequent surge in elderly population in India have led to a growing curiosity in the geriatric age group with Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) represent epiphenomena of AD. However, no comprehensive study has been carried out in South East Asia (Kashmir, India), to assess the behavioral and psychological symptoms in subtypes of AD.ObjectivesThe purpose of this study was to assess BPSD in early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD).Material and MethodsThe study was conducted in the Memory clinic of the postgraduate department of psychiatry, Government Medical College, Kashmir, India from January 2012 to March 2014. The diagnosis of AD patients was done according to NINCDS-ADRDA criteria. A total of 80 patients of AD were screened (40 with age of onset less than 65, and 40 with age of onset greater than 64). Neuropsychiatric inventory (NPI) was the instrument used for evaluating symptoms of BPSD. The data was analyzed using paired t-test.ResultsThe mean age of presentation of EOAD and LOAD was 63.10 years and 84.28 years, respectively, and the difference between the two was found to be statistically significant. The LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances (NBD) than the EOAD group (p ≤.0001).ConclusionThe behavioral and psychological symptoms are significantly severe in late onset subtype compared to the early onset subtype of Alzheimer’s disease in the Kashmiri (Indian) population.

Amyloid beta 1–42 and tau in the cerebrospinal fluid of renal failure patients for the diagnosis of Alzheimer′s disease

Cerebrospinal fluid (CSF) Aβ42, total tau and phosphorylated tau (p-tau) are well-defined diagnostic markers for Alzheimer's disease (AD). There has been no previous report of the use of these markers in the diagnosis of AD in patients with chronic kidney disease (CKD). We would like to report our preliminary findings on these biomarkers in three patients with renal failure. One patient with a clinical diagnosis of AD showed elevated CSF tau, p-tau 181, and decreased Aβ42 levels, within a similar range as in local Chinese AD patients without renal impairment. The other two delirious patients, who did not have a clinical diagnosis of AD, showed normal CSF biomarkers. We found that the diagnosis of AD with CSF biomarkers appears to be useful in renal failure patients. But our results need to be confirmed in a larger study, comparing these CSF biomarkers in AD vs. non-AD patients with concomitant CKD.

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo (N=732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94), p=0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.

Regulation of tau phosphorylation in Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous dementing disorder of the elderly that is characterized by progressive cognitive impairments and the accumulation of abundant amyloid or senile plaques (SPs) and neurofibrillary tangles (NFTs) as well as the massive loss of neurons in the AD brain. Indeed, a secure diagnosis of AD in patients with a chronic progressive dementia requires evidence of numerous SPs and NFTs in the postmortem brain. Although the deposition of fibrillar amyloid or A beta-peptides in extracellular plaques and the accumulation of tau-rich intraneuronal NFTs are not restricted exclusively to AD, there is a close correlation between the burden of tau-rich neurofibrillary lesions in selected telencephalic regions of the brain and the dementia in AD. Since the formation of neurofibrillary lesions from hyperphosphorylated tau proteins may compromise the function and viability of neurons in the AD brain, this review summarizes recent insights into mechanisms that regulate the phosphorylation state of tau in AD.

Reduced plasma oestrogen stimulated neurophysin and delayed response to oestrogen challenge in Alzheimer's disease

Plasma concentrations of oestrogen stimulated neurophysin (ESN) were reduced in 28 patients with Alzheimer's disease (AD) compared with 14 age-matched controls, 16 patients with other presenile dementias and 12 patients with major depressive disorder. The ESN response to oestrogen challenge was delayed in 10 AD patients compared with 7 age-matched controls. Reduced basal and oestrogen stimulated plasma ESN may be related to impaired responsiveness of the hypothalamo-neurohypophysial neurons and/or a reduction in the amount of pituitary ESN available for release. Plasma ESN measurements may be of value for excluding the diagnosis of AD in patients with dementia who present before the age of 65.