Author: Brian Paquette

Physician or non-physician clinician | Premium

Intervention Strategies for APOE ε4 Carriers: Ranking the Evidence, Including What Failed
ByBrian Paquette September 6, 2026

Two randomized trials have now tested whether APOE ε4 carriers benefit more from multidomain lifestyle intervention than non-carriers. FINGER’s prespecified subgroup analysis returned an interaction estimate of 0.023 with a confidence interval crossing zero; US POINTER, with 2,111 participants, returned P=.95 for interaction. The carrier-advantage claim used to justify ε4-specific protocols is not supported. This review ranks what does have evidence — and gives equal space to the trials that failed.

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Physician or non-physician clinician | Premium

Laboratory Assessment for APOE ε4 Carriers: What the Evidence Supports
ByBrian Paquette September 6, 2026

In 4,807 older adults, statin initiation was associated with a 40% lower risk of incident Alzheimer disease among APOE ε4 carriers (HR 0.60, 95% CI 0.49–0.74) and no measurable benefit in non-carriers (HR 0.96; interaction p=0.015). It is one of the few genotype-stratified laboratory findings that survives scrutiny — and it does not produce an APOE-specific lipid target. This assessment separates the tests with evidence behind them from those being marketed to carriers.

Read More Laboratory Assessment for APOE ε4 Carriers: What the Evidence Supports
Non-physician and family education

I Have APOE4. What Do I Do Now?
ByBrian Paquette August 25, 2026August 26, 2026

US POINTER found the same benefit for ε4 carriers as non-carriers (P=.95 for interaction). The MIND diet trial was negative. ACHIEVE was null overall. And the one omega-3 signal in Alzheimer’s trial data appeared only in ε4 non-carriers. A neurologist and ε4 carrier grades the evidence behind each recommendation — including the trials that did not work.

Read More I Have APOE4. What Do I Do Now?
Non-physician and family education

Navigating Pre-Death Grief: Managing the Emotional Toll of Dementia Caregiving
ByBrian Paquette August 21, 2026

Pre-death grief affects up to 71% of dementia caregivers and can exceed the grief felt after death. Evidence-based strategies — mindfulness, CBT, support groups, respite, and palliative care integration — that help caregivers navigate this ambiguous loss.

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Literature Reviews | Non-physician and family education | Physician or non-physician clinician

APOE ε2, ε3, and ε4: How Two Amino Acid Substitutions Produce Three Different Clinical Phenotypes
ByBrian Paquette August 21, 2026September 7, 2026

LDL cholesterol rises linearly across APOE genotype, but coronary risk does not follow it. Bennet et al. (JAMA 2007; n=86,067) found a 44 mg/dL spread between the genotype extremes — and a coronary odds ratio in ε4 carriers of just 1.06 (95% CI 0.99–1.13). Three separate risk quantities are routinely quoted interchangeably in clinic, and only one of them belongs in a disclosure conversation.

Read More APOE ε2, ε3, and ε4: How Two Amino Acid Substitutions Produce Three Different Clinical Phenotypes
Non-physician and family education

APOE 2, 3, and 4: What the Three Versions of This Gene Actually Do
ByBrian Paquette August 21, 2026September 15, 2026

Three versions of one gene, separated by two amino acids — and why that small difference sends Alzheimer’s risk in three different directions.

Read More APOE 2, 3, and 4: What the Three Versions of This Gene Actually Do
Non-physician and family education

APOE ε4 Risk Is Not the Same in Every Population: How Ancestry Changes the Numbers
ByBrian Paquette August 19, 2026September 15, 2026

The widely quoted APOE ε4 risk figures come almost entirely from people of European ancestry. How much the numbers change elsewhere, and the haplotype explanation for why.

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Literature Reviews | Non-physician and family education

Stem Cells, Exosomes, and Peptides for Alzheimer’s Disease: What the Evidence Shows
ByBrian Paquette August 11, 2026August 28, 2026

A randomized phase 2a trial of 49 patients in Nature Medicine found intravenous mesenchymal stem cells slowed whole-brain volume loss by 48.4% in mild Alzheimer’s disease — while the cognitive endpoint’s confidence interval crossed zero. That trial is the entire controlled evidence base for this category. What, then, about the intrathecal infusions, umbilical and Wharton’s jelly preparations, exosome drips, and peptide protocols marketed to ε4 carriers?

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Literature Reviews | Physician or non-physician clinician

Can APOE4 Risk Be Normalized? A Clinical Review
ByBrian Paquette August 8, 2026August 28, 2026

A clinical review of whether APOE ε4-associated risk can be normalized through modifiable intervention — examining multidomain prevention trial evidence, the distinction between relative and absolute risk reduction, and the boundary between what current data support and what they do not.

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Diet and APOE4 | Literature Reviews | Non-physician and family education | Physician or non-physician clinician | Premium

The ε4/ε4 Carriers Who Do Not Develop Alzheimer’s: Resistance and Resilience
ByBrian Paquette August 6, 2026August 28, 2026

A minority of APOE ε4 homozygotes reach advanced age without dementia. This review examines the distinction between resistance to amyloid pathology and resilience despite it, the protective variants and mechanisms implicated to date, and what these exceptional cases do — and do not — establish about modifiable risk in ε4/ε4 carriers.

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