Presence Of Memory Impairment Research Articles

Visual function changes along the continuum of Alzheimer's disease

Aims/Purpose: The progression of Alzheimer's disease (AD) is manifested by a gradual transition from a preclinical phase, characterized by asymptomatic pathological alterations, to an advanced phase of AD accompanied by cognitive impairment. The aim of this study was to explore visual function along the entire AD continuum.Methods: Each participant underwent a comprehensive visual examination, with only visually healthy individuals being selected for the study. The study comprised the following groups: controls (n = 53), positive family history of AD (FH+) (n = 13), mild cognitive impairment (MCI) (n = 23), mild AD (n = 25), and moderate AD (n = 21). The study analysed the results of visual acuity (VA) and contrast sensitivity (CS).Results: A significant reduction in VA was identified between the control group and the MCI, mild AD and moderate AD groups. CS showed significant changes in all cognitive impairment groups compared to the control group and the FH+ group at spatial frequencies of 12 and 18 cpd. In contrast, significant differences were only observed at spatial frequencies of 3 and 6 cpd between the cognitively impaired groups, starting from moderate AD, with no detectable decrease in CS during the MCI phase. No differences were detected between the control group and the FH+ group. The tests showed a positive correlation with the Mini Mental State Examination score and exhibited a favourable predictive ability in the presence of memory impairment, with higher predictive performance observed in the advance stages of AD.Conclusions: The presence of alterations in VA and CS can be observed as early as the MCI stage in individuals with AD. Recognizing the continuum of AD holds significant significance in early detection, with visual examination offering a straightforward and cost‐effective diagnostic tool for AD. Healthcare professionals can leverage this knowledge to gain a better understanding of the progressive nature of the disease.

Memory Performance in Mild Sporadic and Familial Behavioral Variant Frontotemporal Dementia: Findings from the ALLFTD Consortium

AbstractBackgroundMemory impairment is generally considered minimal to absent in those with behavioral variant frontotemporal dementia (bvFTD). We sought to assess the frequencies of subjective and objective memory impairment in individuals with mild bvFTD according to consensus criteria.MethodAssessments were performed in mildly symptomatic bvFTD [defined by global FTLD Clinical Dementia Rating scale (CDR®+NACC FTLD) = 1] mutation carriers (Familial) and non‐mutation carriers (Sporadic) who are participants in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD, www.allftd.org) study. Mutation carriers had a pathogenic mutation in the MAPT, GRN or C9orf72 gene. The presence of subjective memory impairment was defined by a rating >0 on the memory domain of the CDR®+NACC FTLD. Evidence of objective memory impairment was based on performance across 7 memory measures, which include the National Alzheimer’s Coordinating Center Uniform Data Set Version 3 – Craft Story Immediate Recall (CSImm) and Delayed Recall (CSDel), Benson Figure Delayed Recall (BenDel), and the California Verbal Learning Test – Learning (CVLearn), Immediate Recall (CVImm), Delayed Recall (CVDel), and Recognition (CVRecog). Performance was considered abnormal for z‐scores ≤ ‐1.5.ResultData from 38 Familial (mean age 60±8 years, 61% male), and 109 Sporadic (mean age 63±7 years, 70% male) participants were analyzed. Memory ratings >0 on the CDR®+NACC FTLD were common for both Familial (84%) and Sporadic (88%). The frequencies of abnormal performance in the Familial vs Sporadic groups, respectively, per memory measure were: CSImm 43.8% vs 45.9%, p = 0.83; CSDel 46.9% vs 52.6%, p = 0.58; BenDel 29.4% vs 46.4%, p = 0.08; CVLearn 54.8% vs 39.8, p = 0.14; CVImm 64.5% vs 50%, p = 0.16, CVDel 80.6% vs 55.1%, p = 0.01, and CVRecog 51.6 vs 49%, p = 0.80. The frequencies of abnormal performance did not differ (all p>0.05) between Familial and Sporadic for ≥2 tests (79.3% vs 67.7%), ≥4 tests (55.2% vs 44.1%) and ≥6 tests (34.5% vs 31.2%).ConclusionThese data suggest that among those with a mild global severity of bvFTD features: 1) subjective and objective memory impairment are relatively frequent, and 2) the frequency of impairment across memory measures is largely similar between familial and sporadic bvFTD. The presence of memory impairment should not preclude a diagnosis of bvFTD.

A Comprehensive Review on Alzheimer’s Disease its Pathogenesis, Epidermiology, Diagnostics and Treatment

The global impact of Alzheimer's disease (AD) is significant. The current prevalence of Major Neurocognitive Disorder is estimated to affect approximately 44 million individuals. Presently, the United States harbors a population of approximately 6.2 million individuals who are afflicted by Alzheimer's disease (AD) dementia. It is of significance to highlight that mortality associated with Alzheimer's disease (AD) exceeds the combined mortality rates of both breast cancer and prostate cancer. Based on the findings of the National Institute on Aging, the frequency of Alzheimer's disease (AD) exhibits a twofold rise every five years subsequent to attaining the age of 65. Furthermore, with the ongoing process of population aging, an increasingly substantial portion of the population is affected by this particular condition. Based on forecasts, it is anticipated that the United States will experience a financial impact of $355 billion in 2021 as a result of Alzheimer's disease (AD).
 Furthermore, same projections indicate that this amount is expected to increase significantly to over $1.5 trillion by the year 2050. As a result, this would place a significant financial strain on the country. Alzheimer's disease (AD) is a neurodegenerative condition that is distinguished by the existence of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles consisting of hyperphosphorylated τ-protein. The aforementioned abnormal characteristics primarily present themselves inside the cortical and limbic regions of the human brain. The aforementioned ailment is characterized by the presence of memory impairment and a progressive deterioration of neurocognitive abilities. The atypical division of amyloid precursor protein (APP) by β-secretases and γ-secretases leads to the production of Aβ40 and Aβ42 individual molecules, which then undergo the process of oligomerization and aggregation, finally culminating in the formation of senile plaques. The aforementioned disease is additionally aggravated by pathogenic microorganisms, including the human immunodeficiency virus (HIV).
 Moreover, within the framework of disease pathophysiology, the presence of heightened amounts of Aβ peptides within the central nervous system induces the infiltration of microglial cells. Presently, there exists a notable focus within the realm of scientific inquiry on gaining a comprehensive understanding of the pathological nature of Alzheimer's disease (AD) by means of exploring diverse pathways.
 These mechanisms include the abnormal metabolism of tau proteins, the presence of β-amyloid, the inflammatory response, as well as the damage caused by cholinergic dysfunction and free radicals. The ultimate objective of this research is to develop efficacious treatments that can effectively halt or alter the progression of AD. The present study provides an analysis of the pathophysiological mechanisms underlying Alzheimer's disease, as well as an examination of the diagnostic methods employed in its identification. Furthermore, the review explores the many therapy modalities now utilized in managing this neurodegenerative disorder.

Memory Performance in Asymptomatic and Prodromal Familial Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium (P13-6.001)

Memory Performance in Asymptomatic and Prodromal Familial Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium (P13-6.001)

Re‐examining the impact of adjusting for education and sex the RBANS delayed memory score: Implications on the cut‐offs used to detect cognitive impairment in prodromal Alzheimer’s disease. Data from the EPAD‐LCS study.

AbstractBackgroundthe RBANS is a multilingual brief cognitive battery commonly used in both clinical practice and research. Its delayed memory index has been used as entry criteria for clinical trials in early stages of Alzheimer’s disease (AD). Although several studies reported a significant effect of education and sex in RBANS scores, the published normative data only provide adjustments by age. We aimed at exploring the impact of sex and education in the age‐adjusted scores and studying the percentage of change in the classification of memory impairment, along with the association with AD biomarker status after adjusting for education and sex.MethodsWe analyzed data from the EPAD baseline Longitudinal Cohort Study (n = 1,716 [Clinical Dementia Rating [CDR] = 0 n = 1,233; CDR = 0.5 n = 483]), see Table 1. We used multiple regression to assess the impact of years of education and sex on the age‐adjusted delayed memory index within the CDR = 0 sample. The coefficients obtained were used to generate sex‐, education‐ and age‐adjusted scores. The whole sample was classified as having/not having memory impairment (<85 points) with published and full adjusted scores. Within CDR = 0.5 group, the concordance between presence of memory impairment and pathologic amyloid‐β (A+; cut‐off = 1000 pg/ml) and p‐tau levels (T+; cut‐off = 27 pg/ml) in cerebrospinal fluid was assessed.ResultsEducation and sex (being a woman) had significant positive effects (p<0.001) on the age‐adjusted delayed memory scores (Partial eta2 = 0.035 and 0.010). We observed a change of up to 10 points after sex and education adjustment (mean[SD] change = 0.83 [2.6]). The use of fully adjusted scores increased the number of individuals classified as having memory impairment by 1.7%. Within the CDR = 0.5 group, these scores identified 2.5% individuals with memory impairment that were considered within the normal range using the regular norms, and increased the concordance between memory impairment and A+T+ biomarkers by almost 5% (regular norms = 65.2%, adjusted norms = 69.7%).ConclusionAlthough small, education and sex exert a relevant effect in the delayed memory score of the RBANS and improve clinical and biomarker concordance of the conclusions on the cognitive status derived from them. Adding education and sex adjustments to the RBANS measures may improve the selection of individuals for clinical trials.

Association between Intake of Energy and Macronutrients and Memory Impairment Severity in US Older Adults, National Health and Nutrition Examination Survey 2011-2014.

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011–2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have severe memory impairment (OR: 1.52, 95% CI: 1.15 to 2.02; ptrend = 0.005). Specifically, higher energy intake from carbohydrate (OR: 1.59, 95% CI: 1.12 to 2.26) and sugar (OR: 1.54, 95% CI: 1.11 to 2.16) were both significantly associated with the presence of memory impairment. Additionally, higher energy intake from fat, carbohydrate and sugar were significantly associated with more server memory impairment (fat: ptrend = 0.04; carbohydrate: ptrend = 0.03; sugar: ptrend = 0.02). High energy intake, either total or from carbohydrates, fat or sugar, is associated with memory impairment severity in the older US population. No such association was found in energy intake from protein.

Investigation of patient and observer agreement on description of seizures at initial clinical visit.

There have been few studies of agreement between seizure descriptions obtained from patients and observers. We investigated 220 patients and observers who completed structured questionnaires about patients’ semiological seizure features at the initial clinical visit. Inter‐rater reliability was assessed using Cohen’s kappa and indices of positive and negative agreement. Patients and observers had excellent agreement on the presence of memory impairment and generalized shaking and stiffness during seizures. In addition, patients under‐reported seizure descriptions more easily observed externally, whereas observers under‐reported change in patient location at seizure end. These findings may guide interpretation of clinical histories obtain in epilepsy care.

A single seizure selectively impairs hippocampal-dependent memory and is associated with alterations in PI3K/Akt/mTOR and FMRP signaling.

SummaryObjectiveA single brief seizure before learning leads to spatial and contextual memory impairment in rodents without chronic epilepsy. These results suggest that memory can be impacted by seizure activity in the absence of epilepsy pathology. In this study, we investigated the types of memory affected by a seizure and the time course of impairment. We also examined alterations to mammalian target of rapamycin (mTOR) and fragile X mental retardation protein (FMRP) signaling, which modulate elements of the synapse and may underlie impairment.MethodsWe induced a single seizure and investigated hippocampal and nonhippocampal memory using trace fear conditioning, novel object recognition (NOR), and accelerating rotarod to determine the specificity of impairment in mice. We used western blot analysis to examine for changes to cellular signaling and synaptic proteins 1 h, 24 h, and 1 week after a seizure. We also included a histologic examination to determine if cell loss or gross lesions might alternatively explain memory deficits.ResultsBehavioral results indicated that a seizure before learning leads to impairment of trace fear memory that worsens over time. In contrast, nonhippocampal memory was unaffected by a seizure in the NOR and rotarod tasks. Western analysis indicated increased hippocampal phospho‐S6 and total FMRP 1 h following a seizure. Tissue taken 24 h after a seizure indicated increased hippocampal GluA1, suggesting increased α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor expression. Histologic analysis indicated that neither cell loss nor lesions are present after a single seizure.SignificanceThe presence of memory impairment in the absence of damage suggests that memory impairment caused by seizure activity differs from general memory impairment in epilepsy. Instead, memory impairment after a single seizure is associated with alterations to mTOR and FMRP signaling, which leads to a disruption of synaptic proteins involved in consolidation of long‐term memory. These results have implications for understanding memory impairment in epilepsy.

Normal pressure hydrocephalus: Treatable dementia, missed diagnosis—The Launceston Prevalence Study

Normal Pressure Hydrocephalus (NPH) is one of the few treatable forms of dementia, but it is notoriously difficult to diagnose in the elderly. It is often treated by the insertion of ventriculo-peritoneal shunt with significant improvement in the cognitive, gait and urinary functioning. Most studies suggest the condition is rare but there are few studies addressing the prevalence of the condition. We have, therefore, investigated the prevalence of NPH amongst patients with cognitive impairment attending the Memory Disorders Clinic in Launceston. Three hundreds and fifty five consecutive patients were recruited from the Memory Disorders Clinic at the Launceston General Hospital since 2010. The diagnosis of NPH was based on the presence of memory impairment or dementia, and/or balance/gait disorder and the presence of prominent ventricles regardless of cerebral atrophy on MRI of the brain. All patients with NPH were investigated by CSF Flow Study. One hundred and sixty four men and 191 women participated in the study, mean age 73 years (range 32–95 years), mean MMSE score 23 (range 0–30). 190 (54%) patients were diagnosed with mild cognitive impairment, of whom 54 (28%) had underlying anxiety and depression, 23 (12%) had NPH and 9 (5%) had Parkinsonism.165 (46%) were diagnosed with dementia, of whom 77 (47%) had Alzheimer's disease, 33 (20%) had NPH, 20 (12%) had mixed dementia, 9 (5%) had vascular dementia and 26 (16%) were diagnosed with other forms of dementia including Parkinsonism, Lewy Body Disease, Gertsmann Syndrome, and Frontal Lobe Dementia. NPH is probably more common than previously thought. This is important because many patients without shunting might be condemned for years of disabilities and institutionalisation.

Predictive validity and diagnostic stability of mild cognitive impairment subtypes

Mild cognitive impairment (MCI) is subclassified into four subtypes by the presence of impairment in the memory domain (amnestic vs. nonamnestic) and the number of impaired cognitive domains (single vs multiple). However, predictive validity for outcomes of these criteria and the diagnostic stability of the subtypes are questionable. We investigated the outcomes of 140 patients with MCI who participated in the baseline study of the Korean Longitudinal Study on Health and Aging and completed the 18-month follow-up evaluation (mean duration of follow-up = 1.57 ± 0.24 years). We evaluated the predictive validity of the criteria using multinomial logistic regression analyses, and the diagnostic stability of MCI subtypes using annual conversion rates between subtypes. Compared with the single-domain type (MCIs), the multiple-domain type (MCIm) had a lower chance of reversion to normal cognition (MCIm = 10.94%, MCIs = 43.42%) and higher risk of conversion to dementia (MCIm = 23.44%, MCIs = 5.26%). The difference in the reversion rate between the multiple- and single-domain type was statistically significant (odds ratio = 0.233, 95% confidence interval = 0.070-0.771, P = .017). However, neither the chance of reversion nor the risk of conversion was different between amnestic and nonamnestic subtypes. Among the 81 participants who neither converted to dementia nor reverted to normal cognition, 39 converted to different subtype (annual conversion rate = 17.74%). The number of impaired cognitive domains, but not the presence of memory impairment, predicted poor outcomes in people with MCI. However, MCI subtype was diagnostically unstable.

Genetic Variations in CHRNA7 or CHRFAM7 and Susceptibility to Dementia

The presence of memory impairment and cognitive deficits in the Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Pick's disease (PiD) has been associated to dysfunction of cholinergic transmission, possibly due to the loss of cholinergic neurons and to the elimination of nAChR in dementia patients. Alternative hypotheses take into account molecular interactions of the β-amyloid peptide Aβ with nAChR, which may lead to deregulation of the receptor function. Genetic polymorphisms of CHRNA7 and CHRFAM7A, a fusion gene containing a partial CHRNA7 duplication, have been investigated as possible susceptibility traits to dementia, potentially useful either to identify high risk individuals or as therapeutic targets. To summarize the existing evidence, a systematic re-evaluation of published papers has been performed (PubMed database, no language restriction, updated to 1st August 2011). Eleven articles reporting data on genetic variations in CHRNA7 or CHRFAM7 and risk of dementia fulfilled selection criteria and were evaluated. Published evidence on the association between variations in CHRNA7 or CHRFAM7A and the risk of dementia is still sparse and inconclusive. Further studies are needed to establish whether some polymorphisms may really affect the probability of developing AD or other forms of dementia. Additional and more conclusive results may come from the ongoing GWAS studies investigating high numbers of genetic variants in large samples, that have the potential to assess the role of genetic susceptibility in dementia.

Brain Functional Network in Alzheimer's Disease: Diagnostic Markers for Diagnosis and Monitoring

Alzheimer's disease (AD) is the most common type of dementia that is clinically characterized by the presence of memory impairment and later by impairment in other cognitive domains. The clinical diagnosis is based on interviews with the patient and his/her relatives and on neuropsychological assessment, which are also used to monitor cognitive decline over time. Several biomarkers have been proposed for detecting AD in its earliest stages, that is, in the predementia stage. In an attempt to find noninvasive biomarkers, researchers have investigated the feasibility of neuroimaging tools, such as MR, SPECT, and FDG-PET imaging, as well as neurophysiological measurements using EEG. In this paper, we investigate the brain functional networks in AD, focusing on main neurophysiological techniques, integrating with most relevant functional brain imaging findings.

Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study.

The development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76-102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.

Sequence of cognitive decline in dementia in adults with Down's syndrome

AbstractAdults with Down's syndrome (DS) are known to be at risk of dementia of the Alzheimer type (DAT), but because of their lifelong intellectual deficits, it is difficult to determine the earliest signs and characteristics of age‐associated decline and dementia. In a longitudinal study in which all participants were healthy at the time of their entry into the study, the present authors compared the amount of decline on the subtests of the WISC‐R to determine the sequence of cognitive decline associated with varying stages of dementia. Twenty‐two individuals with varying degrees of cognitive decline were compared to 44 adults with DS who have remained healthy. All participants functioned in the mild or moderate range of intellectual disability at initial testing. On each subtest of the WISC‐R, the amount of change experienced by the healthy participants over the study period was compared to the amount of change found for each of the groups with decline. Out of the individuals who showed declines, 10 adults with DS were classified as having ‘questionable’ decline based on the presence of memory impairment, and five and seven adults with DS were classified as in the ‘early stage’ and ‘middle stage’ of DAT, respectively, based on the presence of memory impairment, score on the Dementia Scale for Down Syndrome and a physician's diagnosis. It was found that participants who were identified as ‘questionable’, in addition to the memory loss that determined their classification, also showed significant declines on the Block Design and Coding subtests. The five adults in the early stage of dementia showed declines on these subtests, and in addition, on the Object Assembly, Picture Completion, Arithmetic and Comprehension subtests. The seven adults in the middle stage of dementia showed declines on these subtests, plus declines on Information, Vocabulary and Digit Span subtests. The Picture Arrangement and Similarities subtests were not useful in distinguishing between the groups because of baseline floor effects for a substantial proportion of participants. The present longitudinal study showed a sequence of cognitive decline associated with DAT, beginning with a possible ‘pre‐clinical’ stage, and progressing through the early and middle stages. This approach begins to define the sequence of declining cognitive capacities that contributes to the observed functional deterioration caused by Alzheimer's disease and that is likely to reflect the involvement of cortical areas as the disease progresses.

Memory impairment in schizophrenia: Its' relationship to executive function

The presence of memory impairment in schizophrenia has frequently been documented but much less attention has been given to the qualitative aspects of this impairment and its association to executive function. Using a cognitive-process approach, we examined memory and executive function in 25 patients who met DSM-III-R criteria for schizophrenia. Patients were matched with 25 healthy volunteers. The schizophrenic group was found to have a significant impairment in immediate memory, with relatively spared long-delay memory. Performance on verbal learning and recognition memory was similar to that of controls. Memory deficits were present irrespective of the encoding strategies used and were unrelated to chronicity. In addition, the schizophrenics performed worse than controls on tests of executive function, but the degree of impairment was greater on tests of response initiation and suppression. This pattern of performance resembled that found in patients with subcortical or frontal lesions which was supported by some significant correlations between aspects of memory and executive function. Our results suggest that in schizophrenia, specific executive functions may make a selective contribution to the pattern of memory performance in schizophrenia which is subserved by frontal and to a lesser extent hippocampal/diencephalic systems.

Cerebral atrophy in psychiatric patients.

1. The early clinical symptoms of 40 patients with cerebral atrophy subsequently demonstrated by pneumoencephalogram are reviewed. In 25 cases the earliest abnormalities noted were not memory loss or impairment, but paranoid ideas, depression, neurosis, or psychopathy. 2. Clinical data of the patients with cerebral atrophy were compared with those of a control group who were suspected of having cerebral atrophy, but had normal pneumoencephalograms. The diagnosis of cerebral atrophy is found to be positively correlated with 3 factors: (a) presence of memory impairment by history or examination, (b) presence of abnormal findings on neurological examination, and (c) age over 40. With the absence of any 1of these factors the probability of demonstrating cerebral atrophy radiologically is considerably diminished and with the absence of any 2 the probability becomes extremely small. 3. Cerebral atrophy was found in 5 patients with depression, of the 40-60 age group, without evidence of memory impairment or abnormalities in the neurological examination.