Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAß): A Plasma-Based Biomarker Differentiates Alzheimer's Disease from Other Etiologies of Dementia.

With emerging amyloid therapies, documentation of the patient's amyloid status to confirm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a noninvasive blood-based biomarker utilized to measure Aß oligomerization tendency. We determined the difference in MDS-OAß ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer's disease (AD), (c) non-AD, and (d) mixed Alzheimer's disease-Vascular dementia (AD-VaD). MDS-OAß level was not significantly different between AD and mixed AD-VaD, but both groups were significantly different from the NCI/SCI and from the non-AD group. An MDS-OAß level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD).

Validation of AD8-Philippines (AD8-P): A Brief Informant-Based Questionnaire for Dementia Screening in the Philippines.

AIM: This study was aimed at validating the Filipino version of AD8 (AD8-P). METHODS: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. RESULTS: A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. CONCLUSION: AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline.

Filipino Multicomponent Intervention to Maintain Cognitive Performance in High-Risk Population (FINOMAIN): Study Protocol for a Cluster Randomized Controlled Trial.

Background: More than half of the people with dementia live in lower-middle income countries (LMIC), yet we lack research and evidence-based knowledge to guide health promotion and prevention strategies for cognitive decline. In the Philippines, the prevalence of mild cognitive impairment (MCI) and cardiovascular risk factors among older persons are high, making this population at high risk for developing dementia. This protocol describes a cluster randomized controlled trial that aims to investigate the efficacy of a multicomponent intervention to maintain cognitive performance among high-risk population. Methods: This is a cluster-randomized, two-arm, single-blind trial of a multicomponent intervention that combines dance called INDAK (Improving Neurocognition through Dance and Kinesthetics), nutrition counseling, and vascular risk management. The intervention arm will receive 12 months (1-h, twice per week) of INDAK and every 3 months of nutrition counseling and intensive vascular risk management and monitoring. The control group will receive the usual vascular care advice and referral. A total of 605 (20-25 clusters per arm) community-dwelling Filipino older adults aged ≥ 60 years old with MCI will participate in the study and will be assessed at baseline, 6th- and 12th-month follow-up. The primary outcome is cognitive performance assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), Mnemonic Similarity Tasks (MST), and executive function composite (EFC). Secondary outcomes are functional connectivity assessed through brain imaging, and measures of behavioral, functional level, and quality of life. Discussion: The study aims to provide scientific evidence on a public health intervention that is contextualized in a community setting to reduce dementia risk among older adults with MCI. This model can be an ecological, low-cost, and effective program, thereby conducive to widespread implementation in the Philippines as well as in other low-resource settings with similar public health challenges. The pilot phase was underway with eight villages (clusters), but temporarily interrupted by the pandemic. The full study is anticipated to start after community restrictions are eased.

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis.

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data Sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study Selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data Extraction and Synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main Outcomes and Measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and Relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study Registration: PROSPERO CRD42019119288.

Novel Optineurin Frameshift Insertion in a Family With Frontotemporal Dementia and Parkinsonism Without Amyotrophic Lateral Sclerosis.

Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), granulin precursor (GRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with four members harboring a novel frameshift insertion at OPTN (Chr 10:13166090 G>GA) p.Lys328GluTer11, three of whom presented with FTD-related phenotypes. Additionally, one sibling heterozygous for the frameshift insertion had a predominantly parkinsonian phenotype resembling corticobasal syndrome, but it remains to be determined if this phenotype is related to the frameshift insertion. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.

Dementia Incidence, Burden and Cost of Care: A Filipino Community-Based Study.

Background: In the midst of competing priorities and limited resources in low-middle-income countries (LMIC), convincing epidemiological evidence is critical for urging governments to develop national dementia plans. The majority of primary epidemiological studies on dementia are from high income countries (HIC). Implications for developing countries are typically extrapolated from these outcomes through modeling, meta-analyses, and systematic reviews. In this study, we directly assessed the incidence of dementia, disability adjusted life years (DALYs), and cost of care among community-dwelling Filipino elderly. Methods: This was a follow-up study of the prospective cohort Marikina Memory Ageing Project (MMAP). Baseline assessment was performed in 2011-2012, and follow-up was done in 2015-2016 (N = 748 at follow-up). Incident dementia was determined. Disease burden was computed using the incidence rates and DALYs. Both indirect and direct (medical and non-medical) costs of dementia care were computed. Results: The crude incidence rate was 16 (CI: 13-20) cases per 1,000 person-years (pyr) with 17 (CI: 12-21) per 1,000 pyr for females and 14 (CI: 9-21) per 1,000 pyr for males. Based on this incidence, we project an estimation of 220,632 new cases in 2030, 295,066 in 2040, and 378,461 in 2050. Disease burden was at 2,876 DALYsper 100,000 persons. The economic burden per patient was around Php 196,000 annually (i.e., ~4,070 USD, or 36.7% of average family annual income in the Philippines). The majority (86.29%) of this care expense was indirect cost attributed to estimated lost potential earning of unpaid family caregivers whereas direct medical cost accounted for only 13.48%. Conclusions: We provide the first Filipino community-based data on the incidence of dementia, DALYs, and cost of care to reflect the epidemiologic and economic impact of disease. The findings of this study serve to guide the development of a national dementia plan.

Determining Filipino Normative Data for a Battery of Neuropsychological Tests: The Filipino Norming Project (FNP).

BACKGROUND: Filipino normative data for neuropsychological tests are lacking. OBJECTIVES: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer's Disease Center (UDS-ADC). METHODS: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. RESULTS: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. CONCLUSION: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

Improving Cognition through Dance in Older Filipinos with Mild Cognitive Impairment.

BACKGROUND: People with mild cognitive impairment (MCI) are considered a high-risk population for developing dementia and therefore potential targets for preventive interventions. So far, no pharmacological interventions have proven to be effective. Latest evidence has laid the groundwork for the hypothesis that dancing can have beneficial effect on cognition by improving neuroplasticity. OBJECTIVE: This study aimed to examine whether a structured modular ballroom dance intervention (INDAK) could improve cognition among Filipino older persons with MCI. METHODS: A two-armed, single-blinded, quasi-experimental study was conducted in a community-based population at Marikina City, Philippines. Two hundred and seven participants older than 60 years old with MCI participated through self-assigned allocation to dance (N=101) and control (N=106) groups. The intervention group received INDAK consisting eight types of ballroom dances with increasing complexity lasting one hour, twice a week for 48 weeks. Neurologists and psychologists blinded to the group allocation administered baseline and post intervention assessments using Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog), Filipino version of the Montreal Cognitive Assessment (MoCA-P), Boston Naming Test (BNT), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL) and Disability Assessment for Dementia (DAD). RESULTS: Baseline sociodemographic and clinical characteristics did not differ between groups. The mean differences between baseline and 48-week assessments were compared between dancers and controls, showing that the intervention group improved in ADAS-Cog, MoCA-P, BNT and GDS. CONCLUSION: INDAK is potentially a novel, ecological and inexpensive non-pharmacological intervention that can improve cognition among older Filipinos with MCI.