You can call any of these for free. You do not need a diagnosis, an appointment, or a crisis to call — questions and plain exhaustion are reasons enough.
Alzheimer's Association 24/7 Helpline800-272-390024 hours a day, 365 days a yearFree, confidential support and information for people with dementia, caregivers, families and the public. Master's-level clinicians. Also Spanish.
988 Suicide & Crisis Lifeline98824/7Call or text 988, or chat at 988lifeline.org. For anyone in emotional distress or a mental-health crisis, including caregivers.
Alzheimer's Foundation of America (AFA) Helpline866-232-84849:00 am - 9:00 pm ET, seven days a weekLicensed social workers providing support, info and referrals. Also text message and web chat.Text: 646-586-5283
In a medical emergency, call 911.
More numbers, and what each line does, on the help page.
Which of the 7080 studies in our library other researchers actually build on — measured
two different ways, because the obvious way is misleading on its own.
Read this before the table
Raw citation count rewards being old. A paper published in 2010 has had fifteen years to
collect citations; one published last year has had months. Raw counts also reward being in a big, busy field.
Ranking only by raw count tells you mostly which papers are oldest and most famous — which you probably
already knew.
RCR (Relative Citation Ratio) is the fairer number. It is calculated by the NIH and is
normalised for both field and year: it compares a paper against other papers of the same age in the same
research area. An RCR of 1.0 is exactly average for NIH-funded work in that field and year.
2.0 means roughly twice the citations a typical comparable paper gets; 0.5 means about half.
So: RCR is our primary ranking and answers "most influential for its age and field".
Raw count is the secondary ranking and answers "most cited in absolute terms". Both columns
are shown in every table so you can see where they disagree — and they disagree a lot.
All numbers retrieved 2026-09-27. Citation
counts change daily; a number here is a reading taken on that date, not a permanent property of the paper.
What we could and could not measure
Of 7080 unique studies in the library (after removing duplicates by PubMed ID, then
DOI, then title):
7043 have a citation count from iCite.
6917 have an RCR. RCR cannot be computed until a paper has been out long
enough to accumulate a citation history, so 126 indexed papers —
nearly all of them very recent — have a citation count but no RCR yet.
7060 have a count from OpenAlex, 6998 from
Semantic Scholar.
17 are not indexed in any of the three. These are regulatory
documents, company announcements and conference presentations rather than journal articles.
A paper with no citation data is not a paper with zero citations. It is a paper these
indexes do not cover. Those rows read not indexed below and are never counted
as 0, never averaged in, and never imputed.
The three sources disagree, and we show that rather than hide it
On the 7040 papers where both iCite and OpenAlex returned a number, they gave a
different answer for 6894 of them. The median gap is a factor of
1.3×, and the widest is 728.0×.
That is normal. Each index covers a different set of journals and counts references differently — OpenAlex
indexes preprints and book chapters that iCite does not, for instance. We store every source's number
separately and never average them. The ranking columns below are labelled with the source they come
from; the other sources' numbers are in the downloadable data.
Everything in the library, including biomarker, imaging, genetics and laboratory papers.
These dominate the top of the list — which is itself the reason the prevention view exists.
Most influential — ranked by RCR
40 with an RCR
Field- and time-normalised. 1.0 is the NIH-funded average for that field and year.
Source: iCite (NIH), retrieved 2026-09-27.
These 1984 criteria describe how to diagnose probable, possible, and definite Alzheimer's disease clinically, noting that no laboratory test can determine the diagnosis and that other causes of dementia must be excluded. They are diagnostic guidance, not a treatment or prevention for the disease.
Summary
Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
Key findings
There are no motor, sensory, or coordination deficits early in the disease.
The diagnosis cannot be determined by laboratory tests.
These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence.
Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy.
The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
This is the primary Phase 3 Clarity AD trial report for lecanemab. In 1,795 people with early Alzheimer's disease randomized to lecanemab or placebo every two weeks for 18 months, lecanemab slowed decline on the main dementia-severity scale (CDR-SB) by a small but statistically significant amount (change of 1.21 vs 1.66 points, a difference of 0.45 points on an 18-point scale). Infusion reactions occurred in about a quarter of patients, and brain swelling (ARIA-E) occurred in about 1 in 8.
Adjusted mean CDR-SB change: 1.21 (lecanemab) vs 1.66 (placebo); difference −0.45 (less decline with lecanemab)
Infusion-related reactions in 26.4% of participants; ARIA-E (brain swelling/effusion) in 12.6%
Effect size
Adjusted mean CDR-SB change 1.21 (lecanemab) vs. 1.66 (placebo); difference -0.45
Evidence strength
moderate
Study design / n
phase-3-trial · n = 1,795
Limitations
Modest absolute effect size (0.45 points on an 18-point scale) of debated long-term clinical meaningfulness; high rates of infusion reactions (26.4%) and ARIA-E (12.6%); 18-month duration does not establish long-term outcomes.
This 2005 paper introduced the Montreal Cognitive Assessment (MoCA), a brief screening test, and compared it with the MMSE in 94 people with mild cognitive impairment, 93 with mild Alzheimer's and 90 healthy older adults. At a cutoff of 26, the MoCA picked up 90% of the MCI group (MMSE 18%) and all of the mild Alzheimer's group (MMSE 78%), but it also flagged more healthy people: specificity was 87% versus 100% for the MMSE. It is a screening test that signals who needs a fuller assessment, not a diagnosis, and the authors note that MCI itself is "evolving and somewhat controversial".
Summary
Objectives To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Design Validation study. Setting A community clinic and an academic center. Participants Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). Measurements The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Results Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). Conclusion MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
Key findings
Results Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects.
Presymptomatic Alzheimer's disease can now be identified through blood biomarkers under revised diagnostic criteria, potentially enabling treatment to begin before cognitive symptoms appear. Blood-based biomarkers are incorporated into the diagnostic framework for the first time, providing an additional method for disease identification beyond cerebrospinal fluid and PET imaging.
Summary
This Alzheimer's Association workgroup paper proposes a major update to how Alzheimer's disease is diagnosed: it defines the disease by biological markers (amyloid plaques and tau tangles detected via blood, CSF, or PET) rather than requiring clinical symptoms like memory loss to be present. It also introduces a numeric staging system tracking biomarker and clinical severity together.
Key findings
Alzheimer's disease can now be diagnosed based on biomarker evidence alone, even before symptoms appear
Introduces staging system integrating biological and clinical/functional severity
Incorporates blood-based biomarkers into the diagnostic biomarker categories for the first time
Evidence strength
moderate
Limitations
This is an expert consensus/framework document, not an empirical study with its own participants or effect size.
This Global Burden of Disease analysis estimates how many people had dementia worldwide in 2019 and forecasts the number for 2050. It attributes the projected rise mainly to population growth and population ageing: growth contributed most in sub-Saharan Africa, and ageing contributed most in east Asia. The authors say the country-level estimates can inform national planning, and they call for scaling up interventions on modifiable risk factors alongside research on biological mechanisms. It is a projection of case numbers, not a test of any treatment.
Summary
Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia. Funding Bill & Melinda Gates Foundation and Gates Ventures.
Key findings
Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia.
Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group.
Country-level estimates can be used to inform national planning efforts and decisions.
Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia.
Funding Bill & Melinda Gates Foundation and Gates Ventures.
This 2024 report says there are fewer caregivers than a decade earlier and that each remaining caregiver provides more care. It also reports that unpaid caregivers face an increased risk of emotional distress and of worse mental and physical health. This is an association, not proof that caregiving causes it. The record gives no figures and tests no treatment, so it describes the caregiving burden rather than showing what reduces it.
Summary
These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Its costs, however, extend to unpaid caregivers' increased risk for emotional distress and negative mental and physical health outcomes.
Key findings
These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver.
Its costs, however, extend to unpaid caregivers' increased risk for emotional distress and negative mental and physical health outcomes.
These 2011 expert recommendations revised the 1984 criteria for diagnosing Alzheimer's disease dementia, and were designed to be usable by general healthcare providers without brain scans, spinal-fluid tests or detailed memory testing. The authors state that clinical assessment "will continue to be the cornerstone of the diagnosis in clinical practice"; biomarker evidence was added only "for use in research settings", and they note that "much work lies ahead" to validate it. This is a consensus guideline, not a study that tested patients, and it does not address treatment or prevention.
Summary
The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
Key findings
On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis.
We also retained the term possible AD dementia, but redefined it in a manner more focused than before.
Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings.
The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia.
Much work lies ahead for validating the biomarker diagnosis of AD dementia.
This 2018 NIA-AA paper proposes, for research use, defining Alzheimer's disease by biology rather than by symptoms alone. Its authors "envision" that this will give a more accurate picture of "the sequence of events that lead to cognitive impairment" and of the "multifactorial etiology of dementia", but this is a stated aim, not a tested result. The paper reports no patient data and offers no test, treatment or cure.
Summary
We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia.
Key findings
We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia.
This report describes the public health impact of Alzheimer's, including costs and effects on family caregivers. It does not test any treatment or prevention, so it does not directly change how the disease is treated or cured.
Summary
This article describes the public health impact of Alzheimer's disease, including prevalence and incidence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19.
Key findings
This article describes the public health impact of Alzheimer's disease, including prevalence and incidence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society.
These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver.
Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19.
This 2021 Lancet overview (a review, not a new study) reports that dementia prevalence is projected to double in Europe and triple worldwide by 2050, that Alzheimer's risk is 60–80% heritable with APOE the strongest of more than 40 genetic risk loci, and that PET scans and blood tests for amyloid β and phosphorylated tau "show great promise". It says multidomain lifestyle trials "suggest cognitive benefits" in people at increased risk of dementia, but also that lifestyle factors "do not directly affect Alzheimer's disease pathology". Anti-amyloid, anti-tau and anti-inflammatory drugs were in advanced trials when it was written.
Summary
In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer's disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.
Key findings
The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease.
Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia.
In this phase 3 trial of 1736 people with early symptomatic Alzheimer's disease, donanemab, an antibody designed to clear brain amyloid plaque, slowed decline on a cognitive and functional scale compared with placebo over 76 weeks. The trial reported that 23 of 24 gated outcomes were statistically significant, and it was conducted in people selected for amyloid and low/medium or high tau pathology.
Summary
Importance There are limited efficacious treatments for Alzheimer disease. Objective To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. Design, setting, and participants Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023). Interventions Participants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met. Main outcomes and measures The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of .04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes. Results Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, -7.01 to -5.03) in the donanemab group and -9.27 (95% CI, -10.23 to -8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P Conclusions and relevance Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population. Trial registration ClinicalTrials.gov Identifier: NCT04437511.
Key findings
Results Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial.
Of the 24 gated outcomes, 23 were statistically significant.
The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, -7.01 to -5.03) in the donanemab group and -9.27 (95% CI, -10.23 to -8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and -10.2 (95% CI, -11.22 to -9.16) with donanemab and -13.1 (95% CI, -14.10 to -12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population.
The Neuropsychiatric Inventory (NPI) is a questionnaire, answered by "a caregiver familiar with the patient's behavior", that rates how often and how severely a person with dementia shows 10 behaviours, including delusions, hallucinations, agitation/aggression, depression (dysphoria), anxiety and apathy. Screening questions skip the behaviours that are not present, to keep it short. The authors report it was valid and reliable, though this record gives no figures, and it is a way of measuring symptoms, not a treatment.
Summary
We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
Key findings
The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions.
Both the frequency and the severity of each behavior are determined.
Information for the NPI is obtained from a caregiver familiar with the patient's behavior.
Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable.
The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
This study followed patients discharged after COVID-19 and found some had ongoing problems with lung diffusion, anxiety or depression, fatigue, and kidney function. It does not address Alzheimer's disease treatment, cure or prevention.
Summary
After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m 2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m 2 at follow-up.
Key findings
After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness.
Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m 2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m 2 at follow-up.
In 76 people with mild cognitive impairment (MCI) at one Mayo Clinic registry, memory was the main difference from 234 healthy people; their other thinking skills were comparable. Their memory was similar to that of 106 people with mild Alzheimer's disease, but the Alzheimer's group was also worse in other areas. Over time the MCI group declined faster than healthy people but more slowly than the Alzheimer's group. This is an observational study: it gives no conversion rate and tests no treatment.
Summary
Background Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. Objective To characterize clinically subjects with MCI cross-sectionally and longitudinally. Design A prospective, longitudinal inception cohort. Setting General community clinic. Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. Main outcome measures The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. Conclusions Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
Key findings
Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn.
Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable.
However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well.
Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD.
These 1984 criteria describe how to diagnose probable, possible, and definite Alzheimer's disease clinically, noting that no laboratory test can determine the diagnosis and that other causes of dementia must be excluded. They are diagnostic guidance, not a treatment or prevention for the disease.
Summary
Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
Key findings
There are no motor, sensory, or coordination deficits early in the disease.
The diagnosis cannot be determined by laboratory tests.
These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence.
Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy.
The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
This 2005 paper introduced the Montreal Cognitive Assessment (MoCA), a brief screening test, and compared it with the MMSE in 94 people with mild cognitive impairment, 93 with mild Alzheimer's and 90 healthy older adults. At a cutoff of 26, the MoCA picked up 90% of the MCI group (MMSE 18%) and all of the mild Alzheimer's group (MMSE 78%), but it also flagged more healthy people: specificity was 87% versus 100% for the MMSE. It is a screening test that signals who needs a fuller assessment, not a diagnosis, and the authors note that MCI itself is "evolving and somewhat controversial".
Summary
Objectives To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Design Validation study. Setting A community clinic and an academic center. Participants Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). Measurements The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Results Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). Conclusion MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
Key findings
Results Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects.
These 2011 expert recommendations revised the 1984 criteria for diagnosing Alzheimer's disease dementia, and were designed to be usable by general healthcare providers without brain scans, spinal-fluid tests or detailed memory testing. The authors state that clinical assessment "will continue to be the cornerstone of the diagnosis in clinical practice"; biomarker evidence was added only "for use in research settings", and they note that "much work lies ahead" to validate it. This is a consensus guideline, not a study that tested patients, and it does not address treatment or prevention.
Summary
The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
Key findings
On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis.
We also retained the term possible AD dementia, but redefined it in a manner more focused than before.
Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings.
The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia.
Much work lies ahead for validating the biomarker diagnosis of AD dementia.
This 2018 NIA-AA paper proposes, for research use, defining Alzheimer's disease by biology rather than by symptoms alone. Its authors "envision" that this will give a more accurate picture of "the sequence of events that lead to cognitive impairment" and of the "multifactorial etiology of dementia", but this is a stated aim, not a tested result. The paper reports no patient data and offers no test, treatment or cure.
Summary
We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia.
Key findings
We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia.
In 76 people with mild cognitive impairment (MCI) at one Mayo Clinic registry, memory was the main difference from 234 healthy people; their other thinking skills were comparable. Their memory was similar to that of 106 people with mild Alzheimer's disease, but the Alzheimer's group was also worse in other areas. Over time the MCI group declined faster than healthy people but more slowly than the Alzheimer's group. This is an observational study: it gives no conversion rate and tests no treatment.
Summary
Background Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. Objective To characterize clinically subjects with MCI cross-sectionally and longitudinally. Design A prospective, longitudinal inception cohort. Setting General community clinic. Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. Main outcome measures The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. Conclusions Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
Key findings
Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn.
Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable.
However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well.
Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD.
The Neuropsychiatric Inventory (NPI) is a questionnaire, answered by "a caregiver familiar with the patient's behavior", that rates how often and how severely a person with dementia shows 10 behaviours, including delusions, hallucinations, agitation/aggression, depression (dysphoria), anxiety and apathy. Screening questions skip the behaviours that are not present, to keep it short. The authors report it was valid and reliable, though this record gives no figures, and it is a way of measuring symptoms, not a treatment.
Summary
We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
Key findings
The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions.
Both the frequency and the severity of each behavior are determined.
Information for the NPI is obtained from a caregiver familiar with the patient's behavior.
Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable.
The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
This 2004 review describes mild cognitive impairment (MCI) as "an early, but abnormal, state of cognitive impairment" between normal ageing and very early dementia, and argues it can be diagnosed "in a fashion similar to the clinical diagnoses of dementia and AD", presenting an algorithm to identify people with MCI and sort them into subtypes. It notes that studies have documented an "accelerated rate of progression" to dementia and Alzheimer's in people with MCI, but also that the precise definition has been controversial. It proposes criteria rather than testing them on patients, and it reports no treatment.
Summary
The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
Key findings
It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD.
In 2011 an international expert workgroup convened by the National Institute on Aging and the Alzheimer's Association proposed research criteria for a "preclinical" stage of Alzheimer's disease, the years when the disease process "is thought to begin" before dementia is diagnosed. The aim was a "common rubric" for long-term studies to test which factors best predict who moves from normal cognition to mild cognitive impairment and dementia; it is an expert proposal, not a study that tested patients. The authors state the criteria are "solely intended for research purposes and do not have any clinical implications at this time," and that the link between the disease process and symptoms still needs to be clarified.
Summary
The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
Key findings
This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms.
The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia.
We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies.
These recommendations are solely intended for research purposes and do not have any clinical implications at this time.
It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
Before this study, the ubiquitinated protein inside the tau- and alpha-synuclein-negative inclusions of frontotemporal lobar degeneration (FTLD-U) and ALS was unknown. The authors report that it is TDP-43, which they found in an abnormal form ("hyper-phosphorylated, ubiquitinated, and cleaved") only in affected brain and spinal cord regions. They conclude it is "the common pathologic substrate linking these neurodegenerative disorders". The study is about FTLD and ALS, not Alzheimer's disease, and it does not test any treatment, test or prevention.
Summary
Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.
Key findings
Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders.
This is the primary Phase 3 Clarity AD trial report for lecanemab. In 1,795 people with early Alzheimer's disease randomized to lecanemab or placebo every two weeks for 18 months, lecanemab slowed decline on the main dementia-severity scale (CDR-SB) by a small but statistically significant amount (change of 1.21 vs 1.66 points, a difference of 0.45 points on an 18-point scale). Infusion reactions occurred in about a quarter of patients, and brain swelling (ARIA-E) occurred in about 1 in 8.
Adjusted mean CDR-SB change: 1.21 (lecanemab) vs 1.66 (placebo); difference −0.45 (less decline with lecanemab)
Infusion-related reactions in 26.4% of participants; ARIA-E (brain swelling/effusion) in 12.6%
Effect size
Adjusted mean CDR-SB change 1.21 (lecanemab) vs. 1.66 (placebo); difference -0.45
Evidence strength
moderate
Study design / n
phase-3-trial · n = 1,795
Limitations
Modest absolute effect size (0.45 points on an 18-point scale) of debated long-term clinical meaningfulness; high rates of infusion reactions (26.4%) and ARIA-E (12.6%); 18-month duration does not establish long-term outcomes.
This Global Burden of Disease analysis estimates how many people had dementia worldwide in 2019 and forecasts the number for 2050. It attributes the projected rise mainly to population growth and population ageing: growth contributed most in sub-Saharan Africa, and ageing contributed most in east Asia. The authors say the country-level estimates can inform national planning, and they call for scaling up interventions on modifiable risk factors alongside research on biological mechanisms. It is a projection of case numbers, not a test of any treatment.
Summary
Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia. Funding Bill & Melinda Gates Foundation and Gates Ventures.
Key findings
Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia.
Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group.
Country-level estimates can be used to inform national planning efforts and decisions.
Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia.
Funding Bill & Melinda Gates Foundation and Gates Ventures.
In an early 1.5 T MRI study of 12 people with Alzheimer's disease, 4 with multi-infarct dementia and 9 age-matched controls, small bright spots in the deep white matter appeared in about 60% of both the Alzheimer's patients and the controls and were unrelated to high blood pressure or other vascular risk factors. A more extensive smooth "halo" of brightness around the ventricles was more common in Alzheimer's patients (p = .024), and the authors suggest it "may be of diagnostic importance". This is a very small imaging comparison: it does not test a diagnostic rule, a treatment or any way of preventing the disease.
Summary
The type, frequency, and extent of MR signal abnormalities in Alzheimer's disease and normal aging are a subject of controversy. With a 1.5-MR unit we studied 12 Alzheimer patients, four subjects suffering from multiinfarct dementia and nine age-matched controls. Punctate or early confluent high-signal abnormalities in the deep white matter, noted in 60% of both Alzheimer patients and controls, were unrelated to the presence of hypertension or other vascular risk factors. A significant number of Alzheimer patients exhibited a more extensive smooth "halo" of periventricular hyperintensity when compared with controls (p = .024). Widespread deep white-matter hyperintensity (two patients) and extensive, irregular periventricular hyperintensity (three patients) were seen in multiinfarct dementia. Areas of high signal intensity affecting hippocampal and sylvian cortex were also present in five Alzheimer and two multiinfarct dementia patients, but absent in controls. Discrete, small foci of deep white-matter hyperintensity are not characteristic of Alzheimer's disease nor do they appear to imply a vascular cause for the dementing illness. The frequently observed "halo" of periventricular hyperintensity in Alzheimer's disease may be of diagnostic importance. High-signal abnormalities in specific cortical regions are likely to reflect disease processes localized to those structures.
Key findings
A significant number of Alzheimer patients exhibited a more extensive smooth "halo" of periventricular hyperintensity when compared with controls (p = .024).
This 2021 Lancet overview (a review, not a new study) reports that dementia prevalence is projected to double in Europe and triple worldwide by 2050, that Alzheimer's risk is 60–80% heritable with APOE the strongest of more than 40 genetic risk loci, and that PET scans and blood tests for amyloid β and phosphorylated tau "show great promise". It says multidomain lifestyle trials "suggest cognitive benefits" in people at increased risk of dementia, but also that lifestyle factors "do not directly affect Alzheimer's disease pathology". Anti-amyloid, anti-tau and anti-inflammatory drugs were in advanced trials when it was written.
Summary
In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer's disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.
Key findings
The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease.
Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia.
This study found that revised criteria for behavioural variant frontotemporal dementia improved diagnostic accuracy compared with older criteria in a sample with known frontotemporal lobar degeneration. It concerns diagnosis of a different dementia type and does not report a treatment or cure.
Summary
Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration.
Key findings
Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment.
In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration.
This 1993 report from an international workshop convened by the NINDS with support from AIREN set out research criteria for diagnosing vascular dementia, intended "as a guide for case definition in neuroepidemiologic studies" at three levels of certainty: definite, probable and possible. The criteria stress that vascular dementia takes many forms, that a secure diagnosis needs a link in time between stroke and the start of dementia, and that brain imaging and memory-and-thinking tests should support the diagnosis. The authors say the criteria "await testing and validation and will be revised as more information becomes available"; the report studied no patients and gives no accuracy figures.
Summary
Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
Key findings
Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features.
A library that never mentions these is less trustworthy, not more. A correction usually
means a number or a figure was fixed — it does not mean the paper was withdrawn. A retraction does.
Retracted
Retraction Note: A specific amyloid-β protein assembly in the brain impairs memory.Nature, 2024 ·
retraction notice
· PubMed 38914864
This is the retraction notice. It retracts: Nature. 2006 Mar 16;440(7082):352-7. doi: 10.1038/nature04533.
Corrected after publication
Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.The Lancet Neurology, 2025
· PubMed 40818474
Long-Term Effect of Intensive vs Standard Blood Pressure Control on Mild Cognitive Impairment and Probable Dementia in SPRINT.Neurology, 2025
· PubMed 39819096
Correction published: Neurology. 2025 May 27;104(10):e213686. doi: 10.1212/WNL.0000000000213686.
APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease.Nature Medicine, 2024
· PubMed 38710950
Health System, Community-Based, or Usual Dementia Care for Persons With Dementia and Caregivers: The D-CARE Randomized Clinical Trial.JAMA, 2025
· PubMed 39878968
Correction published: JAMA. 2025 May 6;333(17):1549. doi: 10.1001/jama.2025.4753.
Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction.Alzheimer's & Dementia, 2025
· PubMed 40172303
Cholinesterase inhibitors and memantine are associated with a reduced mortality in nursing home residents with dementia: a longitudinal observational study.Alzheimer's Research & Therapy, 2024
· PubMed 38812028
Correction published: Alzheimers Res Ther. 2024 Aug 5;16(1):178. doi: 10.1186/s13195-024-01548-y.
Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death.JAMA Network Open, 2024
· PubMed 38709531
Correction published: JAMA Netw Open. 2024 Jun 3;7(6):e2424366. doi: 10.1001/jamanetworkopen.2024.24366.
Sleep disorders and the risk of cognitive decline or dementia: an updated systematic review and meta-analysis of longitudinal studies.Journal of Neurology, 2025
· PubMed 41081870
Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.JAMA Internal Medicine, 2015
· PubMed 25961184
Correction published: JAMA Intern Med. 2018 Dec 1;178(12):1731-1732. doi: 10.1001/jamainternmed.2018.6460.
Association of Daily Step Count and Intensity With Incident Dementia in 78 430 Adults Living in the UK.JAMA Neurology, 2022
· PubMed 36066874
Correction published: JAMA Neurol. 2022 Oct 1;79(10):1086. doi: 10.1001/jamaneurol.2022.3612.
Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.European Heart Journal, 2022
· PubMed 36282295
Correction published: Eur Heart J. 2026 Sep 02:ehag701. doi: 10.1093/eurheartj/ehag701.
The efficacy of cognitive stimulation, cognitive training, and cognitive rehabilitation for people living with dementia: a systematic review and meta-analysis.GeroScience, 2024
· PubMed 39485657
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sometimes heavily cited because they were controversial or later disputed — one of the papers in this
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treatment or a behaviour works. For what the studies actually found, read the
research summaries. For decisions about care, talk to a clinician.