Longitudinal changes in awareness over 36 months in patients with mild Alzheimer's disease

ABSTRACTBackground:Longitudinal changes in awareness in dementia have been studied with short follow-up time and mostly in small patient groups (including patients with moderate dementia). We investigated awareness in patients with mild Alzheimer's disease (AD) over 36 months and studied if a decline in awareness was associated with decline in cognition and increase in neuropsychiatric symptoms.Methods:Awareness was measured on a categorical scale in 95 AD patients (age ≥50 years, Mini-Mental State Examination (MMSE) score ≥20). Awareness was rated at three time points (follow-up at 12 and 36 months) where MMSE, Neuropsychiatric Inventory (NPI-Q), and Cornell scale for Depression in Dementia also were applied.Results:At 12 months, 26% had lower awareness rating as compared to baseline and at 36 months lower awareness ratings were found in 39%. At both visits, 16% had higher awareness rating as compared to baseline. Patients with lower awareness at 36 months as compared to baseline had a more rapid increase in NPI-Q score (p = 0.002) over 36 months as compared to patients with stable or improved awareness over 36 months. A more rapid decline in MMSE score was observed for patients with lower awareness at 36 months (as compared to baseline) but only when compared to patients in whom awareness improved over time.Conclusions:The results show essentially no clear relationship between cognitive decline over three years and awareness. In some cases, awareness remained stable or even improved despite significant cognitive decline. In the subgroup where awareness declined over time, overall ratings of neuropsychiatric symptoms declined more rapidly than in the remaining patients.

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Using Digital Speech Assessments to Detect Early Signs of Cognitive Impairment

Frontiers in Digital Health ◽

10.3389/fdgth.2021.749758 ◽

2021 ◽

Vol 3 ◽

Author(s):

Jessica Robin ◽

Mengdan Xu ◽

Liam D. Kaufman ◽

William Simpson

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Screening Tools ◽

Rapid Decline ◽

Assessment Task ◽

Early Signs ◽

Over Time

Detecting early signs of cognitive decline is crucial for early detection and treatment of Alzheimer's Disease. Most of the current screening tools for Alzheimer's Disease represent a significant burden, requiring invasive procedures, or intensive and costly clinical testing. Recent findings have highlighted changes to speech and language patterns that occur in Alzheimer's Disease, and may be detectable prior to diagnosis. Automated tools to assess speech have been developed that can be used on a smartphone or tablet, from one's home, in under 10 min. In this study, we present the results of a study of older adults who completed a digital speech assessment task over a 6-month period. Participants were grouped according to those who scored above (N = 18) or below (N = 18) the recommended threshold for detecting cognitive impairment on the Montreal Cognitive Assessment (MoCA) and those with diagnoses of mild cognitive impairment (MCI) or early Alzheimer's Disease (AD) (N = 14). Older adults who scored above the MoCA threshold had better performance on speech composites reflecting language coherence, information richness, syntactic complexity, and word finding abilities. Those with MCI and AD showed more rapid decline in the coherence of language from baseline to 6-month follow-up, suggesting that this score may be useful both for detecting cognitive decline and monitoring change over time. This study demonstrates that automated speech assessments have potential as sensitive tools to detect early signs of cognitive impairment and monitor progression over time.

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Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

Author(s):

Katja Franke ◽

Christian Gaser

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Aging ◽

Brain Aging ◽

Elderly Subjects ◽

Additional Increase ◽

Longitudinal Changes ◽

Novel Method ◽

The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

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Smell identification test as a progression marker in Alzheimer's disease

European Psychiatry ◽

10.1016/s0924-9338(11)72209-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 502-502

Author(s):

L. Velayudhan ◽

M. Pritchard ◽

S. Lovestone

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Late Onset ◽

Linear Regression Analysis ◽

Rapid Progressors ◽

Progression Marker ◽

Identification Test ◽

Smell Identification

IntroductionFactors influencing or predicting progression in Alzheimer's disease (AD) is not well understood. Olfactory dysfunction, impaired smell identification in particular, is known to occur in AD. Mesial temporal lobe, important for memory function is also critical for the processing of olfactory information. In view of the common anatomical substrate, we hypothesized that olfaction dysfunction worsens faster in people with AD with rapid cognitive decline compared to those with slower cognitive decline.AimsTo test whether smell identification test can be used as a predictor for illness progression in AD patients.MethodsForty one participants with late onset mild to moderate AD were recruited from mental health services for older adults. Subjects were classified as ‘Rapid Progressors’ defined on ‘a-priori’ with a loss of 2 or more points in Mini-Mental State Examination (MMSE) within six months. Assessments included MMSE, Neuropsychiatric Inventory, Bristol Activities of Daily Living, and the University of Pennsylvania Smell Identification Test (UPSIT), at baseline and after 3 months.ResultsTwenty subjects were ‘Rapid Progressors’, and had lower UPSIT scores compared to ‘Non-Rapid Progressors’ both at the baseline (p = 0.02) and at follow up after 3 months (p = 0.05). Baseline UPSIT correlated with follow up UPSIT (r = 0.5, p < 0.01) and MMSE (r = 0.4, p = 0.04). Also it was the baseline UPSIT score that best predicted (p < 0.05) the follow up smell and cognitive function on linear regression analysis.ConclusionsSmell identification function could be useful as a clinical measure to assess and predict progression in AD.

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The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

Journal of Alzheimer s Disease ◽

10.3233/jad-215456 ◽

2021 ◽

pp. 1-12

Author(s):

Heng Zhang ◽

Diyang Lyu ◽

Jianping Jia ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Amyloid Β ◽

Dementia Patients ◽

Positron Emission ◽

Potential Biomarker ◽

Synaptic Degeneration ◽

Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

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Abstract T P160: Influence of Polyunsaturated Fatty Acids on Cognition in Elderly Alzheimer's Disease Patients

Stroke ◽

10.1161/str.46.suppl_1.tp160 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Takashi Yamazaki ◽

Ken Nagata ◽

Daiki Takano ◽

Tetsuya Maeda

Keyword(s):

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Mmse Score ◽

Characteristic Curve ◽

Follow Up Study ◽

Cognitive Stability ◽

The Relationship

Background: Many genes and environmental factors linked to Alzheimer’s disease (AD) risk affect lipid metabolism or the cardiovascular system, strongly implicating cerebrovascular and metabolic dysfunction in AD pathogenesis. Although some PUFAs may improve cognitive function in aging individuals, it is still unclear how different PUFAs influence AD neuropathology and cognitive function. Objective: To examine the influence of polyunsaturated fatty acid (PUFA) metabolism on AD-associated cognitive decline, we investigated the relationship between serum PUFA profile and neuropsychological test performance. Methods: Cognitive functioning in patients with probable AD (n = 174, mean age 77.6 years) was examined using the Mini-Mental State Exam (MMSE) and clock drawing test (CDT). Serum samples were obtained for PUFA profile, including the eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio, and measurement of brain natriuretic peptide (BNP) concentration. In the follow-up study, 47 subjects repeated MMSE and CDT after 1 year, According to the second MMSE score, the subjects were divided into the following 2 groups: those with unchanged or improved MMSE score and those with lower MMSE score. A receiver operating characteristic curve was used to evaluate the relationship between the EPA/AA ratio and 1-year cognitive stability. Results: In the cross-sectional study, total MMSE score correlated positively with the EPA/AA ratio and systolic blood pressure (SBP), and negatively with age and diastolic blood pressure (DBP) (p < 0.05). In the follow-up study, the MMSE score was lower than baseline in 20 subjects, whereas it was improved or unchanged in 29 patients. The EPA/AA ratio in the stable group was significantly greater than that in the deteriorating group, suggesting an association between higher EPA/AA ratio and cognitive stability over 1 year. The EPA/AA ratio predicted stability of cognitive performance with a sensitivity of 66% and specificity of 70% (odds ratio = 4.43) when the cut-off was 0.67. Conclusion: Our results suggest that serum EPA concentration strongly influences cognitive performances in AD patients. The EPA/AA ratio was a sensitive indicator of cognitive stability in this patient group.

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Different patterns of cognitive decline related to normal or deteriorating EEG in a 3-year follow-up study of patients with Alzheimer's disease

Neurology ◽

10.1212/wnl.41.4.528 ◽

1991 ◽

Vol 41 (4) ◽

pp. 528-528 ◽

Cited By ~ 27

Author(s):

E-L. Helkala ◽

V. Laulumaa ◽

H. Soininen ◽

J. Partanen ◽

P. J. Riekkinen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Follow Up Study

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Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610217001879 ◽

2017 ◽

Vol 30 (1) ◽

pp. 103-113 ◽

Cited By ~ 20

Author(s):

N. Siafarikas ◽

G. Selbaek ◽

T. Fladby ◽

J. Šaltytė Benth ◽

E. Auning ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Factor Analysis ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Neuropsychiatric Symptoms ◽

Small Sample ◽

Psychotic Symptoms ◽

Cross Sectional

ABSTRACTBackground:Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD.Methods:This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate–severe AD 441). To compare variables across groups ANOVA or χ2-test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS.Results:The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate–severe AD. We labelled the subgroups “depression,” “agitation,” “psychosis,” and “elation.”Conclusions:The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.

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Automatic Prediction of Cognitive and Functional Decline Can Significantly Decrease the Number of Subjects Required for Clinical Trials in Early Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210664 ◽

2021 ◽

pp. 1-8

Author(s):

Neda Shafiee ◽

Mahsa Dadar ◽

Simon Ducharme ◽

D. Louis Collins ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Cognitive Decline ◽

Functional Decline ◽

Amyloid Β ◽

Cognitive Test ◽

Disease Heterogeneity ◽

Early Alzheimer’S Disease

Background: While both cognitive and magnetic resonance imaging (MRI) data has been used to predict progression in Alzheimer’s disease, heterogeneity between patients makes it challenging to predict the rate of cognitive and functional decline for individual subjects. Objective: To investigate prognostic power of MRI-based biomarkers of medial temporal lobe atrophy and macroscopic tissue change to predict cognitive decline in individual patients in clinical trials of early Alzheimer’s disease. Methods: Data used in this study included 312 patients with mild cognitive impairment from the ADNI dataset with baseline MRI, cerebrospinal fluid amyloid-β, cognitive test scores, and a minimum of two-year follow-up information available. We built a prognostic model using baseline cognitive scores and MRI-based features to determine which subjects remain stable and which functionally decline over 2 and 3-year follow-up periods. Results: Combining both sets of features yields 77%accuracy (81%sensitivity and 75%specificity) to predict cognitive decline at 2 years (74%accuracy at 3 years with 75%sensitivity and 73%specificity). When used to select trial participants, this tool yields a 3.8-fold decrease in the required sample size for a 2-year study (2.8-fold decrease for a 3-year study) for a hypothesized 25%treatment effect to reduce cognitive decline. Conclusion: When used in clinical trials for cohort enrichment, this tool could accelerate development of new treatments by significantly increasing statistical power to detect differences in cognitive decline between arms. In addition, detection of future decline can help clinicians improve patient management strategies that will slow or delay symptom progression.

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Neuropsychiatric Symptoms in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease: A 12-Month Follow-Up Study

Frontiers in Neurology ◽

10.3389/fneur.2021.728108 ◽

2021 ◽

Vol 12 ◽

Author(s):

Thais Bento Lima Da Silva ◽

Tiago Nascimento Ordonez ◽

Allan Gustavo Bregola ◽

Valéria Santoro Bahia ◽

Mário Amore Cecchini ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Neuropsychiatric Symptoms ◽

Linear Regression Analysis ◽

Predictor Variable ◽

Wilcoxon Test ◽

Chi Square ◽

Behavioral Variant Frontotemporal Dementia

Introduction: Neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical managements.Objective: To test whether the Neuropsychiatry Inventory (NPI) could detect change in neuropsychiatric symptoms and caregiver's distress in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) from baseline to a 12-month follow-up and to investigate possible predictors of change in NPI scores.Methods: The sample consisted of 31 patients diagnosed with bvFTD and 28 patients with AD and their caregivers. The Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), the INECO Frontal Screening (IFS), the Frontal Assessment Battery (FAB), the Executive Interview (EXIT-25) and the NPI were applied. Descriptive statistics, Mann-Whitney U test, Wilcoxon test, Chi square (χ2) test and Linear Regression Analysis were used.Results: NPI total and caregiver distress scores were statistically higher among bvFTD patients at both assessment points. MMSE, ACE-R scores significantly declined and NPI Total and Distress scores significantly increased in both groups. In the bvFTD group, age was the only independent predictor variable for the NPI total score at follow up. In the AD group, ACE-R and EXIT-25, conjunctively, were associated with the NPI total score at follow up.Conclusions: In 12 months, cognition declined and neuropsychiatric symptoms increased in bvFTD and AD groups. In the AD group only, cognitive impairment was a significant predictor of change in neuropsychiatric symptoms.

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Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.707580 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wietse A. Wiels ◽

Mandy M. J. Wittens ◽

Dieter Zeeuws ◽

Chris Baeken ◽

Sebastiaan Engelborghs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Depressive Symptoms ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Neuropsychiatric Symptoms ◽

Disease Stage ◽

Research Database ◽

Severe Dementia

Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing “pure” AD to AD with a significant vascular component.Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.

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