INS NYC 2024 Program

Poster	Poster Session 02 Program Schedule 02/15/2024 08:00 am - 09:15 am Room: Shubert Complex (Posters 1-60) Poster Session 02: Aging \| MCI \| Neurodegenerative Disease - PART 1 Final Abstract #14 Neuropsychological Characteristics of a PSEN 1 Variant in the DIAN Argentina Cohort María Clarens, FLENI, Buenos Aries, Argentina Lucia Crivelli, FLENI, Buenos Aries, Argentina Pabllo Bagnati, FLENI, Buenos Aries, Argentina Fernanda Tapajoz, FLENI, Buenos Aries, Argentina Belen Helou, FLENI, Buenos Aries, Argentina Carlos Canyazo, FLENI, Buenos Aries, Argentina Ezewuiel Surace, FLENI, Buenos Aries, Argentina Daniela Romero, Hospital San Bernardo, Salta, Argentina Gabriela Vigo, Hospital San Bernardo, Salta, Argentina Ricardo Allegri, FLENI, Buenos Aries, Argentina Category: Dementia (Alzheimer's Disease) Keyword 1: dementia - Alzheimer's disease Objective: In recent years, there has been an increase in the number of case reports of families with autosomal dominant Alzheimer disease (ADAD) in Latin America. Nevertheless, little is known about clinical phenotypes and demographic characteristics of specific mutations in each country. Past literature has proved that pathogenic variants in LatAm have different and unique features than those reported in Asia, North America and Europe. Clinical heterogeneity in ADAD supports the need to study specific mutations. We aimed to describe the neuropsychological characteristics at baseline assessment of an Argentina PSEN1 p.M146L family enrolled at DIAN. Participants and Methods: Fifteen DIAN participants, positive for the PSEN1 p.M146L mutation, were recruited. DNA was obtained from peripheral blood leukocytes according to standard protocols. In addition, exon 5 of the PSEN1 gene was PCR-amplified, and Sanger sequencing was performed. NACC Uniform Data Set clinical assessment, including the 2.0 UDS Neuropsychological Battery, was administered. 1) Two groups according to disease stages were used to compare initial neuropsychological data: Patients with CDR:0 (n:10) and patients with CDR>0 (n:5) 2) Progression of cognitive symptoms in time were analyzed in a cross-sectional model where each subject represented a stage of disease progression according to the individual expected years to symptom onset. Results: Mean age of Symptom Onset (AAO) for the family was 42.90 (SD: 4,62) . Significant differences were found in several cognitive measures: Logical Memory Inmediate, TMT B and Digit Backward (<0,001); MMSE, Category Fluency Animals, TMT A and Digit Symbol (<0,05). When analyzing the progression of cognitive symptoms in a model according to the estimated age of onset, impaired scores in some neuropsychological tests were found before AAO (Animal Naming, Digit Symbol, and Logical Memory Delay). Conclusions: Differences in neuropsychological tests showed a prevalence of more severe amnestic and dysexecutive symptoms in advanced stages of ADAD for this mutation according to CDR classification. Moreover, impaired scores before symptom onset were found, supporting the need to study the clinical phenotype in this mutation, especially in preclinical stages, in order to develop prodromal neuropsychological markers. Ongoing longitudinal work will be important in tracking changes in this cohort. Further recruitment and assessment over years and inclusion of other characteristics, proper of underrepresented groups, such as socioeconomic status, education, race and ethnicity deserve appropriate follow-up.

Poster

02/15/2024
08:00 am - 09:15 am
Room: Shubert Complex (Posters 1-60)

Poster Session 02: Aging | MCI | Neurodegenerative Disease - PART 1

Final Abstract #14

Neuropsychological Characteristics of a PSEN 1 Variant in the DIAN Argentina Cohort

María Clarens, FLENI, Buenos Aries, Argentina
Lucia Crivelli, FLENI, Buenos Aries, Argentina
Pabllo Bagnati, FLENI, Buenos Aries, Argentina
Fernanda Tapajoz, FLENI, Buenos Aries, Argentina
Belen Helou, FLENI, Buenos Aries, Argentina
Carlos Canyazo, FLENI, Buenos Aries, Argentina
Ezewuiel Surace, FLENI, Buenos Aries, Argentina
Daniela Romero, Hospital San Bernardo, Salta, Argentina
Gabriela Vigo, Hospital San Bernardo, Salta, Argentina
Ricardo Allegri, FLENI, Buenos Aries, Argentina

Category: Dementia (Alzheimer's Disease)

Keyword 1: dementia - Alzheimer's disease

Objective:

In recent years, there has been an increase in the number of case reports of families with autosomal dominant Alzheimer disease (ADAD) in Latin America. Nevertheless, little is known about clinical phenotypes and demographic characteristics of specific mutations in each country. Past literature has proved that pathogenic variants in LatAm have different and unique features than those reported in Asia, North America and Europe. Clinical heterogeneity in ADAD supports the need to study specific mutations. We aimed to describe the neuropsychological characteristics at baseline assessment of an Argentina PSEN1 p.M146L family enrolled at DIAN.

Participants and Methods:

Fifteen DIAN participants, positive for the PSEN1 p.M146L mutation, were recruited. DNA was obtained from peripheral blood leukocytes according to standard protocols. In addition, exon 5 of the PSEN1 gene was PCR-amplified, and Sanger sequencing was performed. NACC Uniform Data Set clinical assessment, including the 2.0 UDS Neuropsychological Battery, was administered.

1) Two groups according to disease stages were used to compare initial neuropsychological data: Patients with CDR:0 (n:10) and patients with CDR>0 (n:5)

2) Progression of cognitive symptoms in time were analyzed in a cross-sectional model where each subject represented a stage of disease progression according to the individual expected years to symptom onset.

Results:

Mean age of Symptom Onset (AAO) for the family was 42.90 (SD: 4,62) . Significant differences were found in several cognitive measures: Logical Memory Inmediate, TMT B and Digit Backward (<0,001); MMSE, Category Fluency Animals, TMT A and Digit Symbol (<0,05). When analyzing the progression of cognitive symptoms in a model according to the estimated age of onset, impaired scores in some neuropsychological tests were found before AAO (Animal Naming, Digit Symbol, and Logical Memory Delay).

Conclusions:

Differences in neuropsychological tests showed a prevalence of more severe amnestic and dysexecutive symptoms in advanced stages of ADAD for this mutation according to CDR classification. Moreover, impaired scores before symptom onset were found, supporting the need to study the clinical phenotype in this mutation, especially in preclinical stages, in order to develop prodromal neuropsychological markers. Ongoing longitudinal work will be important in tracking changes in this cohort. Further recruitment and assessment over years and inclusion of other characteristics, proper of underrepresented groups, such as socioeconomic status, education, race and ethnicity deserve appropriate follow-up.