Butyrylcholinesterase K variant and Alzheimer’s disease

This study attempted to corroborate findings on the association between butyrylcholinesterase K variant and Alzheimer’s disease. This was performed on an autopsy-confirmed series of patients with Alzheimer’s disease and controls. The butyrylcholinesterase K variant was found to be of increased allele frequency in patients with sporadic Alzheimer’s disease. When related to APOE ɛ4 typing the association was specific but not sensitive for the diagnosis of Alzheimer’s disease. Received: 9 June 1998 Received in revised form: 15 September 1998 Accepted: 26 September 1998     

Prevalence and correlates of cognitive asymmetry in a large sample of Alzheimer’s disease patients

Previous research has suggested that a significant minority of patients with Alzheimer’s disease (AD) exhibit asymmetric cognitive profiles (greater verbal than visuospatial impairment or vice versa) and that these patient subgroups may differ in demographic and other characteristics. Prior studies have been relatively small, and this investigation sought to examine correlates of asymmetry in a large patient sample (N = 438). Patients were classified into the following cognitive profile groups: low verbal, symmetric, and low visuospatial. Consistent with past research, 28.3% of participants were classified as having asymmetric cognitive profiles, with more participants in the low visuospatial subgroup. Low visuospatial participants were younger than members of the other subgroups, and low verbal participants performed worse on a measure estimating premorbid verbal intelligence. Findings regarding apolipoprotein E (ApoE) ε4 genotype were equivocal, although results provided some evidence for an effect of the ?4 allele on cognitive asymmetry. These results suggest systematic differences between neuropsychological asymmetry profiles that support the possibility of distinct subgroups of the disease.     

Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer’s disease

Rare variation in the TREM2 gene is associated with a broad spectrum of neurodegenerative disorders including Alzheimer’s disease (AD). TREM2 encodes a receptor expressed in microglia which is thought to influence neurodegeneration by sensing damage signals and regulating neuroinflammation. Many of the variants reported to be associated with AD, including the rare R47H variant, were discovered in populations of European ancestry and have not replicated in diverse populations from other genetic backgrounds. We utilized a cohort of elderly Chinese individuals diagnosed as cognitively normal, or with mild cognitive impairment or AD to identify a rare variant, A192T, present in a single patient diagnosed with AD. We characterized this variant using biochemical cell surface expression assays and found that it significantly altered cell surface expression of the TREM2 protein. Together these data provide evidence that the A192T variant in TREM2 could contribute risk for AD. This study underscores the increasingly recognized role of immune-related processes in AD and highlights the importance of including diverse populations in research to identify genetic variation that contributes risk for AD and other neurodegenerative disorders.     

Prevalence of obstructive sleep apnea in Alzheimer’s disease patients

Journal of Neurology - To assess the prevalence of obstructive sleep apnea (OSA) in patients with mild-moderate Alzheimer’s Disease (AD) and to evaluate cognitive characteristics according to...     

Cell-dependent kinase inhibitor 2A and 2B genetic variability in patients with Alzheimer’s disease

Journal of Neurology -     

Muscle profile and cognition in patients with Alzheimer’s disease dementia

Introduction

Neurodegenerative disease is one of the main contributing factors affecting muscle atrophy. However, this intriguing brain-muscle axis has been explained by the unsubstantial mechanisms. Although there have been several studies that have evaluated the muscle profile and its relation to cognition in patients with dementia, there is still lack of data using standardized methods and only few published studies on Korean populations. The objective of this study is to evaluate the relationship of muscle mass and strength to cognition in patients with Alzheimer’s disease dementia (AD).

Methods

We recruited 91 patients with probable AD without weakness. We assessed patients’ basic demographic characteristics, vascular risk, body mass index, and global cognitive assessment scores. Muscle mass was measured using body dual-energy X-ray absorptiometry. Muscle strength was assessed by isokinetic knee extensor using an isokinetic device at an angular velocity of 60°/s in nm/kg.

Results

The muscle mass and strength were not related to each other in both male and female groups. Only muscle strength, but not muscle mass, was negatively related to cognition. After adjusting for covariates, the relationship between muscle strength and cognition still remained in the male group, however, was attenuated in the female group.

Conclusions

In patients with AD dementia, abundant muscle mass did not mean strong power. The simple lower-extremity muscle strength assessment is more effective in predicting cognition than a muscle mass measure in male patients.

     

SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer’s disease

The neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) is involved in amyloidogenesis, and the SORL1 gene is a major risk factor for Alzheimer’s disease (AD). We investigated AD-related CSF biomarkers for associations with SORL1 genetic variants in 105 German patients with mild cognitive impairment (MCI) and AD. The homozygous CC-allele of single nucleotide polymorphism (SNP) 4 was associated with increased Tau concentrations in AD, and the minor alleles of SNP8, SNP9, and SNP10 and the haplotype CGT of these SNPs were associated with increased SORL1 concentrations in MCI. SNP22 and SNP23, and the haplotypes TCT of SNP19-21-23, and TTC of SNP22-23-24 were correlated with decreased Aβ42 levels in AD. These results strengthen the functional role of SORL1 in AD.     

Posterior cortical atrophy: variant of Alzheimer’s disease?

Abstract Nine patients with posterior cortical atrophy (PCA), a rare degenerative brain disease of unclear etiology and nosology, were followed over a mean time of 7.4 years. The mean age at onset was low (56.2 years). At onset, eight patients had visuo-spatial and eight had memory impairment. A minority showed early signs of occipital lobe involvement with visual agnosia or hemianopia. Eight patients developed dementia after a mean course of five years. 18F-FDG-PET data of six patients were analysed with statistical parametric mapping. They showed hypometabolism centred on the lateral and medial parietal associative cortex, with variable involvement of the adjacent temporal and occipital associative cortex. A minority showed involvement of the frontal lobes, possibly related to deafferenting of areas related to the control of eye movements. Atrophy and hypometabolism were markedly asymmetric in a subset of cases. Autopsy was performed in one patient. Presenile onset, location, and asymmetry of atrophy suggest that PCA represents a biologically separable variant of Alzheimers disease.     

Candidate gene analysis of semaphorins in patients with Alzheimer’s disease

Semaphorins of the SemaIV family are expressed in neurons and decreased in brains from patients with Alzheimer’s disease (AD). Accumulation of an internalized form of Sema3A is associated with degeneration of neurons, making these molecules candidates for the development of AD. Single nucleotide polymorphisms (SNPs) rs36026860 and rs28469467 in Sema3A as well as rs13284404 and rs11526468 in Sema4D were analyzed in a population of 240 patients with AD compared with 222 age-matched controls. None of SNPs in Sema3A were present, either in patients or controls. The distribution of the Sema4D rs11526468 and rs13284404 SNPs was not significantly different between patients and controls, even stratifying for gender or age at onset. In silico analysis predicted that rs11526468 and rs28469467 are probably damaging. This high degree of conservation of Sema3A suggests a very important role for this protein. However, neither Sema3A nor Sema4D likely influence the susceptibility to AD.     

Phosphorylation of soluble tau differs in Pick’s disease and Alzheimer’s disease brains

Frontotemporal lobar degeneration (FTLD) is a common cause of presenile dementia characterised by behavioural and language disturbances. Pick’s disease (PiD) is a subtype of FTLD, which presents with intraneuronal inclusions consisting of hyperphosphorylated tau protein aggregates. Although Alzheimer’s disease (AD) is also characterised by tau lesions, these are both histologically and biochemically distinct from the tau aggregates found in PiD. What determines the distinct characteristics of these tau lesions is unknown. As phosphorylated, soluble tau has been suggested to be the precursor of tau aggregates, we compared both the level and phosphorylation profile of tau in tissue extracts of AD and PiD brains to determine whether the differences in the tau lesions are reflected by differences in soluble tau. Levels of soluble tau were decreased in AD but not PiD. In addition, soluble tau was phosphorylated to a greater extent in AD than in PiD and displayed a different phosphorylation profile in the two disorders. Consistently, tau kinases were activated to different degrees in AD compared with PiD. Such differences in solubility and phosphorylation may contribute, at least in part, to the formation of distinct tau deposits, but may also have implications for the clinical differences between AD and PiD.     

Comparison of olfactory and gustatory disorders in Alzheimer’s disease

Patients with Alzheimer’s disease (AD) develop olfactory and gustatory disorders. However, the order of failure and relevance of the pathophysiology are unclear. We compared olfactory identification and whole mouth gustation in patients with AD to those with mild cognitive impairment (MCI) and to healthy controls (HC) and assessed correlations with pathophysiology. Patients with AD (n = 40), MCI (n = 34), and HC (n = 40) were recruited. We performed the Odor Stick Identification Test for Japanese (OSIT-J), gustatory test by the intraoral dropping method using taste solutions, Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive subscale Japanese version (ADAS-J cog), Touch Panel-type Dementia Assessment Scale (TDAS), and measurement of amyloid β (Aβ) 42 and phosphorylated tau (p-tau) 181 levels in cerebrospinal fluid (CSF). Patients with AD and MCI had lower OSIT-J scores than did the HC. The OSIT-J score was correlated with the MMSE, ADAS-J cog, TDAS, and Aβ42 results. There were no significant differences in the gustatory test scores among the three groups. The gustatory test score was only correlated with the MMSE, ADAS-J cog, and TDAS results. Olfactory function decreased in AD and MCI patients and was associated with CSF biomarker levels and cognitive disorders. The results suggest that olfactory function is impaired in early stage of AD. Gustatory function was not correlated with CSF biomarkers, which suggests that it may not be impaired in early stage of AD.     

Biomarkers in the diagnosis and prognosis of Alzheimer’s disease

Journal of Neurology -     

Parkinson’s disease in patients and obligate carriers of Gaucher disease

BackgroundGaucher disease is an autosomal recessive disorder caused by glucocerebrosidase gene mutations. Accumulating evidence from several Parkinson’s disease cohorts of varying ethnicities suggests that glucocerebrosidase mutations even in the heterozygous state (carriers) may be a susceptibility factor for Parkinson’s. Very few studies have analyzed the frequency of Parkinson’s in carriers and individuals with Gaucher disease.ObjectiveTo determine frequency of Parkinson’s in patients with Gaucher disease and obligate carriers of glucocerebrosidase mutations and compare it with a control group.MethodsA questionnaire was completed by 100 Ashkenazi Jewish Gaucher patients followed at our center and 109 ethnicity-matched controls with no personal or family history of Gaucher disease.ResultsFrequency of Parkinson’s was higher in Gaucher patients (8/100) than in controls (0/109; P = 0.0024). Frequency of Parkinson’s in obligate carriers (11/200) was higher than controls (6/218), but the difference was not statistically significant (P = 0.215). Average age of onset of Parkinson’s was earlier in Gaucher patients (57.2) than the general population and in obligate carriers (60) when compared with controls (76.8; P = 0.01). The L444P genotype was more frequent in Gaucher patients who reported a parent with Parkinson’s (36.40%) than those who did not (4.50%).ConclusionOur study suggests that the risk for developing Parkinson’s may be higher in affected versus carriers of glucocerebrosidase mutations and suggests that L444P may pose a higher risk of developing Parkinson’s than other mutations. It also confirms previous findings that the age of onset of Parkinson’s associated with glucocerebrosidase mutations is earlier than in the general population.     

Phonetic and phonological aspects of speech in Alzheimer’s disease

ABSTRACT

Background: Alzheimer’s disease (AD) can involve changes in communication and can lead to mutism in severe cases. Oral communication may be impaired by phonetic-motor disorders, such as apraxia of speech (AOS), or by language disorders, such as aphasia. Therefore, the identification of manifestations of AOS and phonemic paraphasias in patients with AD is critical to understanding the communication changes and determining the therapeutic planning.

Aims: To identify the distribution of phonetic–phonological manifestations in older patients with AD and healthy older subjects and assess whether these manifestations indicate the origin of the changes, including a predominantly phonetic-motor origin, a predominantly phonological–linguistic origin, or both.

Methods & Procedures: This cross-sectional study evaluated 90 patients with AD and 30 healthy older volunteers. All of the participants underwent the same repetition task for phonetic and phonological assessments using the current classification of phonetic–phonological manifestations; this classification distinguishes characteristics that are mostly related to AOS from other signs that are mostly related to aphasia. Negative binomial regression analysis was conducted to compare the amount of each manifestation presented by the two groups.

Outcomes & Results: The patients with AD showed significantly more signs of aphasia (self-correction, and vowel and consonant substitutions), AOS (prolonged intervals and extended vowel duration), and AOS or aphasia (distortion, omission, attempts at the syllable level, distorted substitutions, and additions) than the healthy older volunteers.

Conclusions: Older adults with AD presented phonetic and phonological changes of aphasia and AOS and, consequently, limitations in symbolic–linguistic planning and motor planning.     

Clinical and neurocognitive aspects of hallucinations in Alzheimer’s disease

Due to their prevalence, hallucinations are considered as one of the most frequent psychotic symptoms in Alzheimer’s disease (AD). These psychotic manifestations reduce patients’ well-being, increase the burden of caregivers, contribute to early institutionalization, and are related with the course of cognitive decline in AD. Considering their consequences, we provide a comprehensive account of the current state of knowledge about the prevalence and characteristics of hallucinations in AD. We propose a comprehensive and testable theoretical model about hallucinations in AD: the ALZHA (ALZheimer and HAllucinations) model. In this model, neurological, genetic, cognitive, affective, and iatrogenic factors associated with hallucinations in AD are highlighted. According to the ALZHA model, hallucinations in AD first involve trait markers (i.e., cognitive deficits, neurological deficits, genetic predisposition and/or sensory deficits) to which state markers that may trigger these experiences are added (e.g., psychological distress and/or iatrogenic factors). Finally, we provide recommendations for assessment and management of these psychotic manifestations in AD, with the aim to benefit patients, caregivers, and health professionals.     

Weak central coherence in patients with Alzheimer’s disease

Central coherence refers to the ability to interpret details of information into a whole.To date,the concept of central coherence is mainly used in research of autism,Asperger’s syndrome and recently in the research on eating disorders.The main purpose of the present study was to examine central coherence in patients with Alzheimer’s disease.Nine Alzheimer’s disease patients and ten age-and gender-matched control subjects,who differed significantly in neurological assessment,were shown a picture of a fire.Compared to control subjects,the Alzheimer’s disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire.In conclusion,patients with Alzheimer’s disease are at the weak end of central coherence,and hence suffer from a fragmented view of their surroundings.The findings have important clinical implications for the understanding of patients with Alzheimer’s diseaseand also for the possibility of caregivers to meet the Alzheimer’s disease individual in an appropriate way in the everyday care.