Elaborated spaced-retrieval and prospective memory in mild Alzheimer's disease

Prospective memory, or the timely remembering of a planned action, is conceptualised as a cognitive process demanding episodic memory and executive attention. Impairments in these skills are characteristic of the cognitive decline in early Alzheimer's disease, providing an expectation of prominent prospective memory difficulties in this population, and yet surprisingly, memory performance in early Alzheimer's disease has rarely been evaluated within a prospective memory framework. In a preliminary study we demonstrated that older adults with early Alzheimer's disease (n=14), as compared to healthy older adults (n=14), were significantly impaired in a simple experimental paradigm of prospective remembering (a text-reading task). In a subsequent intervention study, we investigated the efficacy of spaced-retrieval for improving the prospective remembering performance of older adults with early Alzheimer's disease (n=16) compared to healthy older adults (n=16) under two learning conditions: a spaced-retrieval technique alone or spaced-retrieval combined with elaborated encoding of task. The majority of the Alzheimer's disease group (63%) demonstrated benefit in prospective remembering in the combined condition as compared to spaced-retrieval alone. Participants with Alzheimer's disease who demonstrated better executive attention (Trail Making- set-shifting) and/or better retrospective memory (Hopkins Verbal Learning Test-Revised- recognition) were more successful in the combined learning condition.     

Prospective memory and subjective memory decline: A neuropsychological indicator of memory difficulties in community-dwelling older people

Introduction: Prospective memory difficulties are known to occur in Alzheimer’s disease, and may provide an early indicator of cognitive decline. Older people reporting high levels of subjective memory decline (SMD) but without evidence of cognitive decline on standard neuropsychological tests are increasingly considered at increased risk for Alzheimer’s disease. Therefore, the objective of this study was to investigate whether prospective memory performance is differentially impaired in older people reporting high levels of SMD as compared to a control group. Method: A total of 195 community-dwelling older adults (M_age = 73.48 years) were assessed for self-reported complaints of memory decline and allocated to either a group reporting high levels of SMD (SMD, n = 96) or a healthy control group (HC, n = 99). Groups were assessed on neuropsychological tests, an experimental prospective memory task (focal vs. nonfocal cue conditions), and a naturalistic prospective memory task. Results: The groups did not differ in performance on standard neuropsychological tests of working memory, executive attention, and episodic retrospective memory. Furthermore, on an experimental task of prospective memory (the Supermarket Shopping Trip task), although performance of both groups was better when cues for prospective memory were focal to the ongoing activity (η² = .35), the SMD group were not impaired relative to the control group. On a naturalistic prospective memory task, however, there was a small but significant effect, with the SMD group performing more poorly than the HC group (η² = .02). Conclusions: In older adults with high levels of SMD, naturalistic measures of prospective memory provide an approach to assessing memory performance that can offer a means of investigating the memory complaints of people with SMD. Identifying prospective memory difficulties in SMD also offers a focus for intervention.     

A Meta‐Analysis of fMRI Activation Differences during Episodic Memory in Alzheimer's Disease and Mild Cognitive Impairment

Functional MRI (fMRI) has the potential to be used as a tool to detect biomarkers related to classifying Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Previous meta‐analyses suggest that during episodic memory tasks, MCI patients exhibit hyperactivation in the medial temporal lobe (MTL) while AD patients exhibit hypoactivation, compared to healthy older adults (HOAs). However, these previous studies have methodological weaknesses that limit the generalizability of the results. This quantitative meta‐analysis re‐examines the activation associated with episodic memory in AD and MCI as compared to cognitively normal populations to assess these commonly cited activation differences. A whole‐brain activation likelihood estimation based meta‐analysis was conducted on fMRI studies that examined episodic memory in HOA (n = 200), MCI (n = 131), and AD populations (n = 89; total n = 409). Diffuse activation was exhibited in the HOA sample, while activation was more limited in the clinical populations. Additionally, the HOA sample showed more activation in the right hippocampus compared to the AD sample. The MCI studies showed greater activation in the cerebellum compared to the HOA sample, potentially indicating a compensatory mechanism for verbal encoding. MTL hypoactivation in the AD sample is consistent with previous studies, but more evidence of MCI hyperactivation is needed before considering MTL activation as an early biomarker for the AD disease process.     

Prospective memory on a novel clinical task in older adults with mild cognitive impairment and subjective cognitive decline

Despite the relevance of prospective memory to everyday functioning and the ability to live independently, prospective memory tasks are rarely incorporated into clinical evaluations of older adults. We investigated the validity and clinical utility of a recently developed measure, the Royal Prince Alfred Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented, community-dwelling sample of 257 older adults (mean age = 80.78?years, 67.7% female) with amnestic mild cognitive impairment (aMCI, n = 18), nonamestic mild cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83) despite intact performance on traditional episodic memory tests, and healthy controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse than controls on the RPA-ProMem and its subtasks (time-based, event-based, short-term, long-term). Also, those with SCD scored significantly lower than controls on long-term, more naturalistic subtasks. Additional results supported the validity and inter-rater reliability of the RPA-ProMem and demonstrated a relation between test scores and informant reports of real-world functioning. The RPA-ProMem may help detect subtle cognitive changes manifested by individuals in the earliest stages of dementia, which may be difficult to capture with traditional episodic memory tests. Also, assessment of prospective memory can help guide the development of cognitive interventions for older adults at risk for dementia.     

Virtual Week: Translation and adaptation for the Italian population

The present study adapted a computerised version of Virtual Week, a laboratory measure of prospective memory designed to simulate the kinds of prospective memory tasks encountered in daily life. In particular, this study aimed to translate and adapt Virtual Week for an Italian population. We collected data from 198 subjects that were divided into five groups based on age: young-young adults (20–29 years, n?=?47), young adults (30–45 years, n?=?32), middle-age adults (46–59 years, n?=?32), young-old adults (60–69 years, n?=?41), and old-old adults (70 years plus, n?=?39). Results showed that PM performance was best in younger adults, relatively stable over middle adulthood and then decreased with age, with older adults performing the least accurately, in particular for the time-based condition. Results also demonstrated good reliability estimates across a range of ages and task types. Thus, the adaptation of Virtual Week into Italian appears to be a reliable measure of prospective memory for the Italian population.     

Associative recognition in mild cognitive impairment: Relationship to hippocampal volume and apolipoprotein E

Associative memory involves remembering relations between items of information and is critically dependent on the hippocampus, a brain structure that shows early changes in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease. We examined associative and item memory in aMCI with a focus on the role of medial-temporal lobe regions and genetic risk for Alzheimer's disease. Twenty-four individuals with aMCI and 21 demographically matched healthy older adults underwent associative recognition testing, structural brain imaging, and apolipoprotein E (ApoE) genotyping. A significant interaction between group and recognition type indicated poorer associative recognition than item recognition across tasks in the aMCI group relative to controls. Within the aMCI group, associative but not item recognition showed sizable and significant correlations with hippocampal volume (but not with other medial temporal-lobe structures) and with number of ApoE ε4 alleles. Correlations were smaller and generally not significant in the control group. Our findings replicate and extend previous studies by showing an associative recognition impairment in aMCI that is not accounted for by an item recognition deficit, is related to structural integrity of the hippocampus, and increases with genetic risk for Alzheimer's disease.     

Tau and β-Amyloid Burden Predict Actigraphy-Measured and Self-Reported Impairment and Misperception of Human Sleep

Alzheimer''s disease is associated with poor sleep, but the impact of tau and β-amyloid (Aβ) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Aβ predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received ¹⁸F-FTP-tau and ¹¹C-PIB-Aβ PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Aβ, was associated with markedly worse objective sleep. In contrast, Aβ and tau were associated with worse self-reported sleep quality. Of clinical relevance, Aβ burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals underestimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Aβ deposition are linked with distinct phenotypes of real-world sleep impairment, one that includes a cognitive misperception of their own sleep health.SIGNIFICANCE STATEMENT Alzheimer''s disease is associated with sleep disruption, often before significant memory decline. Thus, real-life patterns of sleep behavior have the potential to serve as a window into early disease progression. In 89 cognitive healthy older adults, we found that tau burden was associated with worse wristwatch actigraphy-measured sleep quality, and that both tau and β-amyloid were independently predictive of self-reported sleep quality. Furthermore, individuals with greater β-amyloid deposition were more likely to underestimate their sleep quality, and sleep quality underestimation was associated with worse executive function. These data support the role of sleep impairment as a key marker of early Alzheimer''s disease, and offer the possibility that actigraphy may be an affordable and scalable tool in quantifying Alzheimer''s disease-related behavioral changes.     

Olfaction and apathy in Alzheimer's disease,mild cognitive impairment,and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.     

Dementia Following Herpes Zoster Encephalitis

We studied the rare case of an older adult with dementia following herpes zoster encephalitis (HZE). This 71-year-old woman presented to us approximately 1 year following resolution of a rapid-onset episode of HZE, and subsequently underwent neuropsychological and neuroimaging examinations. Cognitive assessment revealed impairments in general cognitive functioning, verbal and nonverbal memory, executive functions, speed of information processing, attention/working memory, and motor skills. The patient's neuroimaging data, when compared to a demographically similar healthy control sample (n = 9), demonstrated moderate central and perisylvian brain volume loss, several subcortical lesions in the white matter, and resting state whole brain and hippocampal hypoperfusion. These findings highlight neuropsychological changes evident in a dementia syndrome of this type, and they suggest that early identification and treatment of HZE has implications for the preservation of long-term cognitive functioning.     

Naturalistic prospective memory in older adults: Predictors of performance on a habitual task

Age-related difficulties in episodic prospective memory (PM) are common. However, little is known about habitual PM, which involves remembering to carry out intended actions that are regular and repeated. This is important for many health-related tasks and for maintaining independence in daily living activities. This study investigates, in older people, the predictors of habitual PM performance in a naturalistic setting. A group of 191 community-based, older adults (aged 65–89 years) wore an actigraph over two weeks. The habitual PM task involved pressing a button twice daily (Bed-time, Rise-time) on the actigraph. Accuracy of response was calculated for Bed-time and Rise-time, determined by light, movement, and diary data. The contribution of retrospective memory and executive function to PM performance was assessed. PM was more accurate at Bed-time compared to Rise-time (p?<?.01), and better in the first compared to the second week (p?<?.01). Retrospective memory contributed small but significant unique variance (β?=?.24) to PM accuracy. For older adults living in the community, both contextual factors (e.g., time of day) and retrospective memory are important for individuals’ ability to remember to perform daily tasks. This is relevant when planning interventions for maintaining independent living in ageing.     

Effects of aging and of Alzheimer's disease on verbal memory

Abstract

This study aimed to define the verbal memory profiles of very old normal subjects and subjects with Alzheimer's Disease, and to identify verbal memory indices having the highest discriminant power. Forty-three old normal subjects (mean age = 71 years, SD = 3, range = 65–75), 39 very old normal subjects (mean age = 81 years, SD = 4, range = 76–87), and 45 Alzheimer's patients (mean age = 70 years, SD = 5, range = 59–78) received the Rey test of verbal memory and the WAIS-R Digit Span forward and backward. All but one of the indices could distinguish very old from Alzheimer's subjects. A discriminant analysis disclosed a verbal memory profile of Alzheimer type in 15.4% of the very old group and of very old type in 16.2% of the Alzheimer's patients. Rate of forgetting, immediate and delayed Rey indices, and the true positive responses were, in decreasing order, the main determinants of the discriminant function. Thus, all of the components of verbal memory are differently affected by aging and Alzheimer's disease and contribute to define individual verbal memory profiles.     

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Down's syndrome is a chromosomal disorder that invariably results in both intellectual disability and Alzheimer's disease neuropathology. However, only a limited number of studies to date have investigated intrinsic brain network organisation in people with Down's syndrome, none of which addressed the links between functional connectivity and Alzheimer's disease. In this cross‐sectional study, we employed ¹¹C‐Pittsburgh Compound‐B (PiB) positron emission tomography in order to group participants with Down's syndrome based on the presence of fibrillar beta‐amyloid neuropathology. We also acquired resting state functional magnetic resonance imaging data to interrogate the connectivity of the default mode network; a large‐scale system with demonstrated links to Alzheimer's disease. The results revealed widespread positive connectivity of the default mode network in people with Down's syndrome (n = 34, ages 30–55, median age = 43.5) and a stark lack of anti‐correlation. However, in contrast to typically developing controls (n = 20, ages 30–55, median age = 43.5), the Down's syndrome group also showed significantly weaker connections in localised frontal and posterior brain regions. Notably, while a comparison of the PiB‐negative Down's syndrome group (n = 19, ages 30–48, median age = 41.0) to controls suggested that alterations in default mode connectivity to frontal brain regions are related to atypical development, a comparison of the PiB‐positive (n = 15, ages 39–55, median age = 48.0) and PiB‐negative Down's syndrome groups indicated that aberrant connectivity in posterior cortices is associated with the presence of Alzheimer's disease neuropathology. Such distinct profiles of altered connectivity not only further our understanding of the brain physiology that underlies these two inherently linked conditions but may also potentially provide a biomarker for future studies of neurodegeneration in people with Down's syndrome.     

Yes/No Versus Forced-Choice Recognition Memory in Mild Cognitive Impairment and Alzheimer's Disease: Patterns of Impairment and Associations with Dementia Severity

Memory tests are sensitive to early identification of Alzheimer's disease (AD) but less useful as the disease advances. However, assessing particular types of recognition memory may better characterize dementia severity in later stages of AD. We sought to examine patterns of recognition memory deficits in individuals with AD and mild cognitive impairment (MCI). Memory performance and global cognition data were collected from participants with AD (n?=?37), MCI (n?=?37), and cognitively intact older adults (normal controls, NC; n?=?35). One-way analyses of variance (ANOVAs) examined differences between groups on yes/no and forced-choice recognition measures. Individuals with amnestic MCI performed worse than NC and nonamnestic MCI participants on yes/no recognition, but were comparable on forced-choice recognition. AD patients were more impaired across yes/no and forced-choice recognition tasks. Individuals with mild AD (≥120 Dementia Rating Scale, DRS) performed better than those with moderate-to-severe AD (<120 DRS) on forced-choice recognition, but were equally impaired on yes/no recognition. There were differences in the relationships between learning, recall, and recognition performance across groups. Although yes/no recognition testing may be sensitive to MCI, forced-choice procedures may provide utility in assessing severity of anterograde amnesia in later stages of AD. Implications for assessment of insufficient effort and malingering are also discussed.     

Immediate memory and electrophysiologic effects of prefrontal cortex transcranial direct current stimulation on neurotypical individuals and individuals with chronic traumatic brain injury: a pilot study

Purpose/aim: Memory impairment post-TBI is common, frequently persistent, and functionally debilitating. The purposes of this pilot study were to assess and to compare immediate behavioral auditory working memory and electrophysiologic effects of three different, randomized, conditions of left dorsolateral prefrontal cortex (LDLPFC) transcranial direct current stimulation (tDCS) applied to four neurotypical adults and four adults with chronic traumatic brain injury (TBI). Materials/methods: Pre- and post-anodal, cathodal, and sham tDCS auditory memory performance, auditory event-related potentials (P300 amplitude and latency) and power of alpha and theta EEG bands were measured across individuals in each group. Results: Post-anodal tDCS only, the neurotypical and TBI groups both demonstrated significantly improved immediate auditory memory function. Also post-anodal tDCS, the TBI group demonstrated significantly increased P300 amplitude versus post-sham tDCS. The neurotypical group demonstrated no pre- post-tDCS electrophysiologic changes across conditions. Conclusions: These findings are consistent with findings of other studies of immediate tDCS effects on other types of memory in neurotypical individuals and in individuals with Parkinson's disease, Alzheimer's disease and stroke and suggest that individuals with memory impairments second to chronic TBI may benefit from LDLPFC anodal tDCS. Pairing tDCS with traditional behavioral memory interventions may facilitate TBI rehabilitation outcomes and warrants continued investigation.     

Locus coeruleus neuron density and parkinsonism in older adults without Parkinson's disease

Previous work has showed that nigral neuron density is related to the severity of parkinsonism proximate to death in older persons without a clinical diagnosis of Parkinson's disease (PD). We tested the hypothesis that neuron density in other brain stem aminergic nuclei is also related to the severity of parkinsonism. We studied brain autopsies from 125 deceased older adults without PD enrolled in the Memory and Aging Project, a clinicopathologic investigation. Parkinsonism was assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). We measured neuron density in the substantia nigra, ventral tegmental area, locus coeruleus, and dorsal raphe, along with postmortem indices of Lewy body disease, Alzheimer's disease and cerebrovascular pathologies. Mean age at death was 88.0 years, and global parkinsonism was 14.8 (SD, 9.50). In a series of regression models that controlled for demographics and neuron density in the substantia nigra, neuron density in the locus coeruleus (estimate, ?0.261; SE, 0.117; P = .028) but not in the ventral tegmental area or dorsal raphe was associated with severity of global parkinsonism proximate to death. These findings were unchanged in models that controlled for postmortem interval, whole‐brain weight, and other common neuropathologies including Alzheimer's disease and Lewy body pathology and cerebrovascular vascular pathologies. In older adults without a clinical diagnosis of PD, neuron density in locus coeruleus nuclei is associated with the severity of parkinsonism and may contribute to late‐life motor impairments. © 2012 Movement Disorder Society     

The Philadelphia Brief Assessment of Cognition (PBAC): A Validated Screening Measure for Dementia

The Philadelphia Brief Assessment of the Cognition (PBAC) is a brief dementia-screening instrument. The PBAC assesses five cognitive domains: working memory/executive control; lexical retrieval/language; visuospatial/visuoconstructional operations; verbal/visual episodic memory; and behavior/social comportment. A revised version of the PBAC was administered to 198 participants including patients with Alzheimer's disease (AD) (n?=?46) and four groups of patients with frontotemporal dementia (FTD) syndromes: behavioral-variant FTD (bvFTD; n?=?65), semantic-variant primary progressive aphasia (PPA) (svPPA; n?=?22), non-fluent/agrammatic-variant PPA (nfaPPA; n?=?23), and corticobasal syndrome (CBS; n?=?42), and a group of normal controls (n?=?15). The total PBAC score was highly correlated with the MMSE. The criterion validity of the PBAC was assessed relative to standard neuropsychological test performance. Using standard neuropsychological test performance as a criterion, the total PBAC score accurately identified the presence and severity of dementia. Intra-class correlations between PBAC subscales and standard neuropsychological tests were highly significant. PBAC subscales demonstrated good clinical utility in distinguishing AD and FTD subtypes using receiver operating characteristic analysis and standard diagnostic performance statistics to determine optimal subscale cut scores. The PBAC is a valid tool and able to assesses differential patterns neuropsychological/behavioral impairment in a broad range of neurodegenerative conditions.     

High apolipoprotein E ε4 allele frequency in Age-related memory decline

Many studies have demonstrated a strong association between the presence of one or two ε4 alleles and Alzheimer's disease (AD), although few data are available on the apolipoprotein E (APOE) ε4 frequencies at the preclinical stages of AD. Thus, with a view to determining whether APOE genotyping could be useful in the early detection of AD, we determined the APOE allele frequencies in patients with memory complaints without dementia (age-related memory decline, ARMD). We found an APOE ε4 allele frequency of 0.315 in the ARMD group, similar to 0.293 in the AD group, in contrast to 0.057 in the control group. Significant differences (t= ?2.91, df=25,p=0.008) were found between the Alzheimer's Disease Assessment Scale (ADAS) total scores in the ARMD patients with at least one ε4 allele (mean=24.2) compared with the ARMD patients without the ε4 allele (mean= 14.7). Our results suggest that the patients with memory complaints, a high ADAS score, and the presence of one or two APOE-4 alleles could be at high risk for developing AD. Thus, we propose that genotyping in conjunction with the ADAS scale may prove useful as diagnostic markers of AD in the presymptomatic stages.     

Deficits on Corsi's block-tapping task in early stage Parkinson's disease

Cognitive deficits in Parkinson's disease (PD) include disturbances in working memory. We examined sequential visuo-spatial memory span by means of an adaptation of the Corsi Block-Tapping Task in groups of medicated (n=14) and non-medicated (n=15) patients with early stage PD, and in control subjects (n=22). A deficit in memory span was found in medicated patients with early stage PD relative to controls. There were no differences between non-medicated patients relative to either controls or medicated patients. A decrease in sequential visuo-spatial memory span appears to be a relatively early feature of PD and most likely reflects executive rather than mnemonic dysfunction.